Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 266
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Osteoporos Int ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39093437

RESUMEN

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. METHODS: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. RESULTS: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (ß-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. CONCLUSION: 68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

2.
Endocr Pract ; 30(3): 239-245, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38122932

RESUMEN

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.


Asunto(s)
Hiperparatiroidismo Primario , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada Cuatridimensional/métodos , Hiperparatiroidismo Primario/diagnóstico por imagen , Colina , Tecnecio Tc 99m Sestamibi , Glándulas Paratiroides/diagnóstico por imagen , Radiofármacos
3.
Mol Genet Genomics ; 298(3): 683-692, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36971833

RESUMEN

To study the effects of low-density lipoprotein receptor-related protein 5 (LRP5) gene mutations on bone, and to open up our view of LRP5 and Wnt pathways on bone mass regulation. Three patients with increased bone mineral density or thickened bone cortex were included, who were 30-year-old, 22-year-old and 50-year-old men, respectively. The latter two patients were son and father of a same family. The characteristics of bone X-rays were evaluated in detail. Bone turnover markers were detected, such as procollagen type 1 amino-terminal peptide (P1NP), alkaline phosphatase (ALP), and type 1 collagen carboxyl terminal peptide (ß-CTX). Dual energy X-ray absorptiometry (DXA) was used to measure the bone mineral density (BMD) at lumbar spine and proximal femur of the patients. The targeted next-generation sequencing (NGS) technology was used to detect pathogenic gene mutations, which were further verified by Sanger sequencing. Moreover, the gene mutation spectrum and phenotypic characteristics of reported patients with LRP5 gain-of-function mutations were summarized by reviewing the literature. The main characteristics of the first patient were headache, facial paralysis, high BMD (lumbar vertebrae 1-4: 1.877 g/cm2, Z-score: 5.8; total hip: 1.705 g/cm2, Z-score: 5.7), slightly increased P1NP (87.0 ng/mL) and ß-CTX (0.761 ng/mL) level, and with thickened bone cortex, especially the cranial vault. The latter two patients showed enlargement of the mandible and enlarged osseous prominence of the tours palatinus. X-rays showed that the bone cortex of skull and long bones were thickened. The bone turnover markers and BMD were normal. All three cases carried novel missense mutations in LRP5 gene, which were mutation in exon 3 (c.586 T > G, p.Trp196Gly) of the first patient, and mutation in exon 20 (c.4240C > A, p.Arg1414Ser) of the latter two patients. Combined with the reported literature, a total of 19 gain-of-function mutations in LRP5 were detected in 113 patients from 33 families. Hotspot mutations included c.724G > A, c.512G > T and c.758C > T. Furthermore, mutations in the exon 3 of LRP5 may cause severe phenotypes. LRP5 gain-of-function mutations can lead to rare autosomal dominant osteosclerosis type Ι (ADO Ι), which was characterized by increased bone mass and thickened bone cortex. In-depth research on the Wnt pathway will be benefit for discovering important mechanisms of bone mass regulation.


Asunto(s)
Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad , Osteosclerosis , Humanos , Huesos , Densidad Ósea/genética , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Mutación , Osteosclerosis/diagnóstico por imagen , Osteosclerosis/genética , Masculino , Persona de Mediana Edad
4.
Osteoporos Int ; 34(8): 1453-1464, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37202541

RESUMEN

Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients. PURPOSE: The primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients. METHODS: Twenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated. RESULTS: Compared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength. CONCLUSION: PHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients.


Asunto(s)
Osteoartropatía Hipertrófica Primaria , Humanos , Masculino , Radio (Anatomía)/diagnóstico por imagen , Tibia/diagnóstico por imagen , Densidad Ósea , Huesos , Absorciometría de Fotón
5.
Calcif Tissue Int ; 112(1): 13-23, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36261652

RESUMEN

Achondroplasia (ACH) is a skeletal disorder caused by fibroblast growth factor receptor 3 (FGFR3) variants. Volumetric bone mineral density (vBMD), bone microarchitecture, and strength have not been evaluated in these patients previously. This study aims to evaluate vBMD, bone microarchitecture, and strength in ACH patients. Seventeen patients underwent clinical and biochemical evaluations, and genetic testing. High-resolution peripheral quantitative computed tomography was performed in 10 ACH patients and 21 age- and sex-matched healthy subjects. All individuals had the hotspot mutation of c.1138G > A in FGFR3. Linear growth retardation, disproportionate short stature, and genu varum are the most common manifestations. The mean height was 108.82 ± 24.08 cm (Z score: - 5.72 ± 0.96). Total vBMD in the ACH and the control groups was 427.08 ± 49.29 mg HA/cm3 versus 300.35 ± 69.92 mg HA/cm3 (p < 0.001) at the radius and 336.90 ± 79.33 mg HA/cm3 versus 292.20 ± 62.35 mg HA/cm3 (p = 0.098) at the tibia; both at the radius and tibia, vBMD of trabecular bones was significantly lower in the ACH group than in the control group, but vBMD of cortical bones was slightly higher in the ACH group. Trabecular separation and cortical thickness in the ACH group were significantly higher than those in the control group, but trabecular number was significantly decreased in the ACH group. Stiffness and failure load were only better at the radius in the ACH group. ACH patients have higher total and cortical vBMD, lower trabecular vBMD, worse trabecular bone microarchitecture, thicker cortical bone thickness, and better estimated bone strength.


Asunto(s)
Acondroplasia , Densidad Ósea , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos , Humanos , Absorciometría de Fotón , Acondroplasia/genética , Acondroplasia/metabolismo , Densidad Ósea/genética , Estudios Transversales , Mutación , Radio (Anatomía) , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Tibia , Huesos/anatomía & histología , Huesos/fisiología
6.
Calcif Tissue Int ; 113(5): 483-495, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37704776

RESUMEN

This study aims to investigate the influence of overweight/obesity and change in weight or body mass index (BMI) on incident fractures among Chinese postmenopausal women. According to BMI, 754 postmenopausal women were categorized into normal weight (NW), overweight (OW), and obesity (OB) groups, respectively. We used data from the baseline and the second survey for statistical analysis, including anthropometric data, clinical fractures, and morphometric vertebral fractures (MVFs) assessed by X-rays. The prevalence of previous MVFs was 32.7% and 21.8% in the OB and NW groups, respectively (p < 0.05). All incident fractures and incident MVFs accounted for 10.7 and 6.3% among all participants within five years. Overweight/obesity and increase in weight or BMI during the follow-up had no associations with all incident fractures, incident MVFs, and incident clinical non-VFs among all participants. However, after multivariate adjustment, the increased BMI at baseline was the risk factor of incident MVFs in the OW group (odds ratio, OR 2.06, 95% confidence interval, 95% CI 1.16-3.66, p = 0.014), and increase in weight (OR 0.89, 95% CI 0.79-0.99, p = 0.036) or BMI (OR 0.77, 95% CI 0.59-0.99, p = 0.045) during the follow-up were the protective factors of all incident fractures in the NW group. Overweight/obesity and change in weight or BMI do not correlate with fracture risk in postmenopausal women, but an increase in weight is the protective factor against incident fractures in normal-weight participants. Overweight postmenopausal women with a higher BMI should pay attention to the risk of MVFs.


Asunto(s)
Fracturas Óseas , Fracturas de la Columna Vertebral , Femenino , Humanos , Índice de Masa Corporal , Fracturas de la Columna Vertebral/etiología , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Posmenopausia , Beijing , Obesidad/complicaciones , Obesidad/epidemiología , Fracturas Óseas/complicaciones , Factores de Riesgo
7.
BMC Musculoskelet Disord ; 24(1): 309, 2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37076878

RESUMEN

INTRODUCTION: Osteoporosis leads to more serious consequences in men than in women, but less is known about its impacts on health-related quality of life (HRQoL) of men, and whether the anti-osteoporosis treatment can improve HRQoL of men with osteopenia/osteoprosis. METHODS: We enrolled men with primary osteoporosis and age-matched healthy controls. We collected medical history, serum levels of carboxyl-terminal type I collagen telopeptide, procollagen type I propeptides, and bone mineral density of patients. All patients and controls completed the short-form 36 (SF-36) questionnaires. Changes in HRQoL of osteopenia/osteoporosis men were prospectively evaluated after alendronate or zoledronic acid treatment. RESULTS: A total of 100 men with primary osteoporosis or osteopenia and 100 healthy men were included. The patients were divided into three subgroups: osteopenia (n = 35), osteoporosis (n = 39) and severe osteoporosis (n = 26). Men with osteoporosis or severe osteoporosis had impaired HRQoL in domains of physical health compared to healthy controls. HRQoL scores in physical health related domains of patients with severe osteoporosis were significantly lower compared to healthy controls, and were the poorest among the three subgroups of patients. Fragility fracture history was correlated with lower SF-36 scores about physical health. In 34 men with newly diagnosed osteoporosis receiving bisphosphonates treatment, HRQoL scores were significantly improved in domains of physical health after treatments. CONCLUSIONS: The HRQoL is significantly impaired in men with osteoporosis, and the more severe the osteoporosis, the poorer the HRQoL. Fragility fracture is an important influencing factor of deteriorated HRQoL. Bisphosphonates treatment is beneficial to improve HRQoL of osteopenia/osteoporosis men.


Asunto(s)
Enfermedades Óseas Metabólicas , Fracturas Óseas , Osteoporosis , Masculino , Humanos , Femenino , Difosfonatos/uso terapéutico , Calidad de Vida , Osteoporosis/tratamiento farmacológico , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Densidad Ósea
8.
Osteoporos Int ; 33(10): 2193-2204, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35767093

RESUMEN

Gitelman syndrome (GS) is the disease model of the inactivation of thiazide-sensitive sodium chloride cotransporter (NCC), which is believed to benefit bone mass and reduce fracture risk. In this study, we found that GS patients have superior bone microarchitecture, which is associated with the disease status. Several decreased bone parameters with aging in healthy controls were reversed in GS patients to a certain extent. PURPOSE: To evaluate the impact of the inactivation of NCC on bone turnover and microarchitecture in Gitelman syndrome patients. METHODS: A cross-sectional study was conducted in 45 GS patients (25 males and 20 females). Serum procollagen type 1 N-terminal propeptide (P1NP), ß-carboxy-terminal crosslinked telopeptide of type 1 collagen (ß-CTX), and osteocalcin were measured. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in GS patients and age- and sex-matched healthy controls. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. RESULTS: GS patients had a relatively lower level of ß-CTX. aBMD at several skeletal sites was improved in GS patients. HR-pQCT assessment revealed that GS patients had slightly thinner but significantly more compact trabecular bone (increased trabecular number and decreased thickness), notably decreased cortical porosity, and increased volume BMD (vBMD) at both the radius and tibia compared with controls. The disease severity, represented as the relationship with the minimum level of magnesium during the course and standard base excess, was associated with bone microarchitecture parameters after adjusting for age, sex, and BMI. The decreased vBMD and Tb.BV/TV, and increased Tb.Sp and Ct.Po with aging, were reversed in GS patients to a certain extent. CONCLUSION: GS patients have superior bone microarchitecture, which suggests that the inactivation of NCC might be beneficial for avoiding osteoporosis.


Asunto(s)
Síndrome de Gitelman , Simportadores , Absorciometría de Fotón , Densidad Ósea/fisiología , Colágeno Tipo I , Estudios Transversales , Femenino , Silenciador del Gen , Humanos , Magnesio , Masculino , Osteocalcina , Procolágeno , Radio (Anatomía)/diagnóstico por imagen , Simportadores del Cloruro de Sodio , Tiazidas , Tibia/diagnóstico por imagen
9.
Calcif Tissue Int ; 111(6): 634-640, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35831717

RESUMEN

X-linked dominant hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets/osteomalacia, is caused by loss-of-function phosphate-regulating endopeptidase homolog X-linked gene (PHEX) variants. However, synonymous PHEX variants are rare in XLH. We report a 7-year-old boy with hypophosphatemia, short stature, and lower limb deformity. Whole-exome sequencing, reverse transcription-polymerase chain reaction, and Sanger sequencing were performed to identify the pathogenicity of the variant. A novel synonymous PHEX variant (NM_000444.4:c.1530 C>T, p.Arg510Arg) was detected in the proband. Further analysis revealed a 58-bp deletion at the 5' site of exon 14 during splicing. This study extends the genetic spectrum of XLH and confirms the rarity and significance of synonymous PHEX variants.


Asunto(s)
Raquitismo Hipofosfatémico Familiar , Enfermedades Genéticas Ligadas al Cromosoma X , Hipofosfatemia , Osteomalacia , Masculino , Humanos , Niño , Raquitismo Hipofosfatémico Familiar/genética , Endopeptidasa Neutra Reguladora de Fosfato PHEX/genética , Exones , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Mutación
10.
Calcif Tissue Int ; 110(4): 451-463, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34988594

RESUMEN

Hyperplastic callus (HPC) is the most conspicuous features of osteogenesis imperfecta (OI) type V, of which accurate diagnosis and treatment are facing challenges. We investigate the clinical features, and impact factors of HPC in OI type V patients. In this retrospective single-center study, a total of 21 patients with type V OI confirmed by IFITM5 mutation were included. Radiological characteristics of bone were evaluated by X-rays, dual-energy X-ray absorptiometry, and computed tomography scan. Bone biopsy specimens were performed and stained by routine hematoxylin-eosin. The effects of bisphosphonates on HPC were investigated. Eleven patients (52.3%) had HPCs at 19 skeletal sites, 11 of which affected the femur. Three patients developed four (21.1%) HPCs after fractures, and 15 (78.9%) HPCs occurred in absence of bone fracture. The progress of HPCs was variable, of which most HPCs enlarged in the initial phase and remained stable, and only one HPC dwindled in size. One patient had a rapidly growing mass on the right humerus, and biopsy showed irregular trabeculae of woven bone and immature bone and cartilage in the loose and edematous collagenous network without signs of tumor. Bisphosphonates treatment had no significant effects on HPC of OI patients. HPC is the specific characteristic of OI type V patients, and its location, shape, size, and progression are variable, and the femur is the most frequently involved site. It is very important to make a diagnosis of HPC through detecting IFITM5 mutation and completing pathological diagnosis if necessary. The treatment of HPC is worth further exploration.


Asunto(s)
Osteogénesis Imperfecta , Difosfonatos/uso terapéutico , Humanos , Proteínas de la Membrana/genética , Osteogénesis Imperfecta/tratamiento farmacológico , Estudios Retrospectivos
11.
Calcif Tissue Int ; 110(4): 518-528, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34800131

RESUMEN

Paget's disease of bone (PDB) is a rare metabolic bone disorder, which is extremely rare in Asian population. This study aimed to investigate the phenotypes and the pathogenic mutations of woman with early-onset PDB. The clinical features, bone mineral density, x-ray, radionuclide bone scan, and serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and ß-carboxy-terminal cross-linked telopeptide of type 1 collagen (ß-CTX) were measured in detail. The pathogenic mutations were identified by whole-exon sequencing and confirmed by Sanger sequencing. We also evaluated the effects of intravenous infusion of zoledronic acid on the bones of the patient and summarized the phenotypic characteristics of reported patients with mutation at position 155 of the valosin-containing protein (VCP). The patient only exhibited bone pain as the initial manifestation with vertebral compression fracture and extremely elevated ALP, P1NP, and ß-CTX levels; she had no inclusion body myopathy and frontotemporal dementia. The missense mutation in exon 5 of the VCP gene (p.Arg155His) was identified by whole-exome sequencing and further confirmed by Sanger sequencing. No mutation in candidate genes of PDB, such as SQSTM1, CSF1, TM7SF4, OPTN, PFN1, and TNFRSF11A, were identified in the patient by Sanger sequencing. Rapid relief of bone pain and a marked decline in ALP, P1NP, and ß-CTX levels were observed after zoledronic acid treatment. Previously reported patients with VCP missense mutation at position 155 (R155H) always had myopathy, frontotemporal dementia, and PDB, but the patient in this study exhibited only PDB. This was the first report of R155H mutation-induced early-onset in the VCP gene in Asian population. PDB was the only manifestation having a favorable response to zoledronic acid treatment. We broadened the genetic and clinical phenotype spectra of the VCP mutation.


Asunto(s)
Fracturas por Compresión , Demencia Frontotemporal , Enfermedades Musculares , Osteítis Deformante , Fracturas de la Columna Vertebral , Femenino , Demencia Frontotemporal/genética , Humanos , Mutación/genética , Osteítis Deformante/tratamiento farmacológico , Osteítis Deformante/genética , Dolor , Profilinas/genética , Proteína que Contiene Valosina/genética , Ácido Zoledrónico
12.
Calcif Tissue Int ; 110(3): 313-323, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34709441

RESUMEN

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia type 1 (MED1) are two rare skeletal disorders caused by cartilage oligomeric matrix protein (COMP) variants. This study aims to analyze the genotype and phenotype of patients with COMP variants. Clinical information for 14 probands was collected; DNA was extracted from blood for COMP variant detection. Clinical manifestations and radiology scoring systems were established to evaluate the severity of each patient's condition. Serum COMP levels in PSACH patients and healthy subjects were measured. Thirty-nine patients were included, along with 12 PSACH probands and two MED1 probands. Disproportionate short stature, waddling gait, early-onset osteoarthritis and skeletal deformities were the most common features. The height Z-score of PSACH patients correlated negatively with age at evaluation (r = - 0.603, p = 0.01) and the clinical manifestation score (r = - 0.556, p = 0.039). Over 50% of the PSACH patients were overweight/obese. The median serum COMP level in PSACH patients was 16.75 ng/ml, which was significantly lower than that in healthy controls (98.53 ng/ml; p < 0.001). The condition of MED1 patients was better than that of PSACH patients. Four novel variants of COMP were detected: c.874T>C, c.1123_1134del, c.1531G>A, and c.1576G>T. Height Z-scores and serum COMP levels were significantly lower in patients carrying mutations located in calmodulin-like domains 6, 7, and 8. As the two phenotypes overlap to different degrees, PSACH and MED1 are suggested to combine to produce "spondyloepiphyseal dysplasia, COMP type". Clinical manifestations and radiology scoring systems, serum COMP levels and genotype are important for evaluating patient condition severity.


Asunto(s)
Acondroplasia , Proteína de la Matriz Oligomérica del Cartílago , Acondroplasia/diagnóstico por imagen , Acondroplasia/genética , Acondroplasia/terapia , Proteína de la Matriz Oligomérica del Cartílago/genética , Proteínas de la Matriz Extracelular/genética , Glicoproteínas , Humanos , Proteínas Matrilinas/genética , Mutación
13.
Phytopathology ; 112(6): 1299-1309, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35000433

RESUMEN

Fusarium pseudograminearum is a soilborne, hemibiotrophic phytopathogenic fungus that causes Fusarium crown rot and Fusarium head blight in wheat. The basic leucine zipper proteins (bZIPs) are evolutionarily conserved transcription factors that play crucial roles in a range of growth and developmental processes and the responses to biotic and abiotic stresses. However, the roles of bZIP transcription factors remains unknown in F. pseudograminearum. In this study, a bZIP transcription factor Fpkapc was identified to localize to the nucleus in F. pseudograminearum. A mutant strain (Δfpkapc) was constructed to determine the role of Fpkapc in growth and pathogenicity of F. pseudograminearum. Transcriptomic analyses revealed that many genes involved in basic metabolism and oxidation-reduction processes were downregulated, whereas many genes involved in metal iron binding were upregulated in the Δfpkapc strain, compared with the wild type (WT). Correspondingly, the mutant had severe growth defects and displayed abnormal hyphal tips. Conidiation in the Fpkapc mutant was reduced, with more conidia in smaller size and fewer septa than in the WT. Also, relative to WT, the Δfpkapc strain showed greater tolerance to ion stress, but decreased tolerance to H2O2. The mutant caused smaller disease lesions on wheat and barley plants, but significantly increased TRI gene expression, compared with the WT. In summary, Fpkapc plays multiple roles in governing growth, development, stress responses, and virulence in F. pseudograminearum.


Asunto(s)
Fusarium , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Perfilación de la Expresión Génica , Peróxido de Hidrógeno , Enfermedades de las Plantas/microbiología , Triticum/genética , Triticum/microbiología , Virulencia
14.
Endocr Pract ; 28(3): 250-256, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34968764

RESUMEN

OBJECTIVE: Osteoporosis in men has been neglected despite its association with disability and mortality. We evaluated the effect of bisphosphonates (BPs) on bone mineral density (BMD) and bone turnover biomarkers of osteoporotic men with different androgen levels. METHODS: This case-control study included 136 osteoporotic men who were divided into normal group (n = 75) and hypogonadism group (n = 61) (patients treated with testosterone were excluded) according to their serum testosterone levels (cutoff value, 350 ng/dL). BMD, serum testosterone, total alkaline phosphatase, and cross-linked C-telopeptide of type I collagen were detected. The relationship between testosterone levels and BMD at baseline was evaluated. All patients were treated with BPs for 2 years. We compared the effects of BPs on BMD and bone turnover biomarkers between the 2 groups. RESULTS: At baseline, there were no significant differences in BMD and bone turnover biomarkers between the 2 groups. Testosterone levels were positively correlated with BMD in the hypogonadism group. After treatment, the lumbar BMD increased by 7.65% ± 1.54% and 7.47% ± 1.88% in normal and hypogonadism groups, respectively (both P < .01 vs baseline) and hip BMD increased without significant differences between the 2 groups. Serum cross-linked C-telopeptide of type I collagen and alkaline phosphatase levels decreased without significant differences between the 2 groups (all P < .01 vs baseline). CONCLUSION: Testosterone level is positively correlated with BMD in men with hypogonadism. In osteoporotic men, BPs significantly increase spine and hip BMD and decrease bone resorption. The efficacy of BPs is similar in men with or without hypogonadism.


Asunto(s)
Andrógenos , Hipogonadismo , Biomarcadores , Densidad Ósea , Remodelación Ósea , Estudios de Casos y Controles , Difosfonatos/farmacología , Difosfonatos/uso terapéutico , Humanos , Hipogonadismo/tratamiento farmacológico , Masculino , Testosterona
15.
BMC Musculoskelet Disord ; 23(1): 1049, 2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36456918

RESUMEN

BACKGROUND: The reduction in androgen level gives rise to a decrease in bone mineral density (BMD) and muscle strength, but the exact mechanisms are unclear. We investigated the roles of novel cytokines of sclerostin and irisin on bone and muscle of orchiectomized rats. METHODS: Twenty 3-month-old male rats were randomized to receive sham or orchiectomy (ORX) operation. Rats were euthanized after 8 weeks of surgery, and serum levels of sclerostin and irisin were measured by enzyme-linked immunosorbent assay at baseline and execution. Grip strength was measured by a grip strength tester at baseline and before execution. BMD and bone microarchitecture were measured by microcomputed tomography. The samples of bone and muscle were harvested at execution. Bone biomechanics were measured by three-point bending tests and vertebral body indentation tests. Bone and muscle histological features were analyzed by hematoxylin and eosin stain, Von Kossa's stain and tartrate resistant acid phosphatase stain. Simple linear regression analyses were used to analyze the relationships between serum levels of sclerostin, irisin and grip strength and BMD of ORX rats. RESULTS: Serum sclerostin level increased from 279 ± 44 pg/mL to 586 ± 57 pg/mL since baseline to 8 weeks after ORX (P = 0.002), which was significantly higher than that in sham rats (406 ± 20 pg/mL at execution) (P = 0.012). Serum irisin level decreased from 4.12 ± 0.20 ng/mL to 3.55 ± 0.29 ng/mL since baseline to 8 weeks of ORX (P = 0.048), which was significantly lower than sham rats (4.84 ± 0.37 pg/mL at execution) (P = 0.013). Trabecular BMD, parameters of bone microarchitecture, bone strength, grip strength and the myofibers size of soleus muscles were significantly lower in ORX rats than in sham group. Grip strength was positively correlated with femoral trabecular BMD (r = 0.713, P < 0.001) and bone volume/total volume (r = 0.712, P < 0.001) in all rats. The serum sclerostin level was negatively correlated to femoral trabecular BMD (r = -0.508, P = 0.022) and grip strength (r = -0.492, P = 0.028). Serum irisin level was positively correlated with femoral trabecular BMD (r = 0.597, P = 0.005), but no obvious correlation was found between irisin level and muscle strength in all rats. CONCLUSIONS: Reduced BMD, impaired bone microarchitecture, weak strength of bone and muscle, and thin myofibers were induced by androgen deficiency of ORX rats. Serum sclerostin and irisin levels were significantly changed after ORX, which might be closely correlated with the occurrence of osteoporosis and sarcopenia in ORX rats.


Asunto(s)
Andrógenos , Fibronectinas , Animales , Masculino , Ratas , Densidad Ósea , Músculos , Microtomografía por Rayos X
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(5): 526-529, 2022 May 10.
Artículo en Zh | MEDLINE | ID: mdl-35598271

RESUMEN

OBJECTIVE: To detect the genetic variant of a child with cleidocranial dysplasia (CCD) and to find out the causation of the illness. METHODS: Gene variant was identified by the second generation targeted sequencing and Sanger sequencing. RESULTS: The gene sequencing revealed that the RUNX2 gene had c.196C>T(p.Glu66*) nonsense variant, which was predicted to be a pathogenic variant according to the ACMG guidelines(PVS1+PS2). CONCLUSION: The variant of c.196C > T in the RUNX2 gene may be the cause of the child with CCD, and the novel variant enriches the RUNX2 gene variant spectrum.


Asunto(s)
Displasia Cleidocraneal , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Pueblo Asiatico/genética , Niño , China , Displasia Cleidocraneal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Humanos , Mutación
17.
Clin Endocrinol (Oxf) ; 95(2): 277-285, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33961300

RESUMEN

OBJECTIVE: Bone responsiveness to parathyroid hormone (PTH) in different subtypes of pseudohypoparathyroidism type 1 (PHP1) remains controversial. We aimed to investigate this phenomenon using bone turnover markers (BTMs) in a large cohort of PHP1 patients. DESIGN: Retrospective study. PATIENTS: Sixty-three PHP1 patients diagnosed by molecular analysis were used as subjects, and 48 sex- and age-matched patients with nonsurgical hypoparathyroidism (NS-HP) were used for comparison. MEASUREMENTS: Bone turnover markers, alkaline phosphatase (ALP), C-terminal telopeptide of type I collagen (ß-CTX) and related parameters in PHP1 were compared among different subtypes and with NS-HP. RESULTS: Among all the PHP1 patients (15 PHP1A, 14 familial 1B and 34 sporadic 1B), 23.8% had elevated baseline BTM levels. No significant difference was found in the ß-CTX levels among different subtypes. The ß-CTX level was positively correlated with the PTH level for all PHP1, PHP1B and PHP1A patients (B = 0.001, 0.001 and 0.004, respectively; all p < .05). The BTM levels of PHP1 patients were significantly higher than those of NS-HP patients (ß-CTX: 0.56 ng/ml vs. 0.20 ng/ml, p = .001; ALP: 105 U/L vs. 72 U/L, p = .001). The serum ß-CTX levels in different PHP1 subtypes were all significantly higher than those in NS-HP patients in adults. Among the 22 followed up patients, changes in BTMs were associated with changes in PTH (ß-CTX: r = .507, p = .023; ALP: r = .475, p = .034). CONCLUSIONS: Bone tissues respond to PTH in different PHP1 subtypes, and it is reasonable to monitor and normalize PTH and BTMs in addition to the serum and urinary calcium levels in the follow-up of PHP1 patients.


Asunto(s)
Hormona Paratiroidea , Seudohipoparatiroidismo , Adulto , Biomarcadores , Remodelación Ósea , Colágeno Tipo I , Humanos , Estudios Retrospectivos
18.
Endocr Pract ; 27(9): 866-873, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33705970

RESUMEN

OBJECTIVE: Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare cause of Cushing's syndrome and diagnosis and management remain challenging. The aim of this study was to present the clinical spectrum of a group of EAS cases in a single center to explore better management strategies. METHODS: A retrospective study was conducted to identify 88 confirmed EAS cases at our hospital from 1984 to 2019. The clinical, biochemical, imaging, and pathological features were analyzed. RESULTS: Of the 88 eligible patients with EAS, 38 (43.2%) cases of pulmonary neuroendocrine tumors (NETs) and a larger number of thymic/mediastinal NETs (29 cases, 33%) were identified. The clinical and biological features of EAS and Cushing's disease overlapped but were more severe in EAS. Inferior petrosal sinus sampling (97.4%) and computed tomography (85.4%) provided the highest positive diagnostic accuracy. Computed tomography is also a useful tool to identify tumors in chest cavity compared with nonchest lesions (91.2% vs 57.1%). Although a greater tumor size (4.54 cm vs 1.44 cm) and higher rate of insuppressible high-dose dexamethasone suppression test (83.3% vs 51.5%) were found in thymic/mediastinum NETs than in pulmonary NETs, the level of hormone production had no difference. CONCLUSION: EAS had more common and severe clinical presentations than Cushing's disease, and multiple imaging approaches are required for reliable diagnosis. A higher proportion of thymic/mediastinal NETs was found in our study. For patients without a certain tumor source, long-term follow-up and further evaluations are needed.


Asunto(s)
Síndrome de ACTH Ectópico , Hormona Adrenocorticotrópica , Síndrome de ACTH Ectópico/diagnóstico , Diagnóstico Diferencial , Humanos , Muestreo de Seno Petroso , Estudios Retrospectivos
19.
Int J Cancer ; 147(9): 2446-2457, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32574388

RESUMEN

Parathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Although some mutations such as CDC73 have been found in patients, the molecular mechanism of PC still needs extensive data to clarify. Whole-genome sequencing (WGS) was performed with frozen samples from 23 PC patients. Peripheral leukocytes were collected from 14 patients and served as controls. Somatic and germline gene alterations, copy number abnormalities and structural variants were detected. Inactivating CDC73 mutations were identified in 39.1% of patients, but only one germline inactivating mutation was found. Other cancer-related mutations identified in more than one case were MAF (2/23), NEB (6/23), NCOR1 (2/23), TTK (2/23), GRIN3A (4/23), TRIO (2/23), MAP1B (2/23), TJP2 (2/23) and FAM20A (2/23). In the seven wild-type CDC73 samples, the mutated genes were enriched in pathways involving antigen presentation, allograft rejection or autoimmune disease. More copy number variants were found in patients with cancer recurrence (P = .006) and CDC73 mutations (P = .022) than in those without these characteristics. PIK3CA loss was found in one sample, which also harboured a CDC73 mutation. Gene alterations in the PI3K/AKT/mTOR pathway were found in 78.3% (18/23) of tumours. The most prominent cancer-predisposing mutations were PDE4DIP (15/23), MAP3K1 (13/23) and CDC42EP1 (10/23). In conclusion, the PI3K/AKT/mTOR pathway may be pivotal in PC. CDC73 mutation correlated with an increased mutational burden and tumour relapse. PC patients with wild-type CDC73 harboured mutations relevant to antigen presentation and autoimmune diseases. A molecular classification based on the CDC73 mutation may help to manage follow-up and therapy for PC patients.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Recurrencia Local de Neoplasia/epidemiología , Neoplasias de las Paratiroides/genética , Adulto , Anciano , Carcinoma/sangre , Carcinoma/patología , Variaciones en el Número de Copia de ADN , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/genética , Glándulas Paratiroides/patología , Glándulas Paratiroides/cirugía , Neoplasias de las Paratiroides/sangre , Neoplasias de las Paratiroides/patología , Neoplasias de las Paratiroides/cirugía , Paratiroidectomía , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Riesgo , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Supresoras de Tumor/genética , Secuenciación Completa del Genoma , Adulto Joven
20.
BMC Med Genet ; 21(1): 214, 2020 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-33129265

RESUMEN

BACKGROUND: Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by progressive kyphoscoliosis, congenital muscular hypotonia, marked joint hypermobility, and severe skin hyperextensibility and fragility. Deficiency of lysyl hydroxylase 1 (LH1) due to mutations of PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) gene has been identified as the pathogenic cause of kEDS (kEDS-PLOD1). Up to now, kEDS-PLOD1 has not been reported among Chinese population. CASE PRESENTATION: A 17-year-old Chinese male patient presenting with hypotonia, joint hypermobility and scoliosis was referred to our hospital. After birth, he was found to have severe hypotonia leading to delayed motor development. Subsequently, joint hypermobility, kyphoscoliosis and amblyopia were found. Inguinal hernia was found at age 5 years and closed by surgery. At the same time, he presented with hyperextensible and bruisable velvety skin with widened atrophic scarring after minor trauma. Dislocation of elbow joint was noted at age of 6 years. Orthopedic surgery for correction of kyphoscoliosis was performed at age 10 years. His family history was unremarkable. Physical examination revealed elevated blood pressure. Slight facial dysmorphologies including high palate, epicanthal folds, and down-slanting palpebral fissures were found. He also had blue sclerae with normal hearing. X-rays revealed severe degree of scoliosis and osteopenia. The Echocardiography findings were normal. Laboratory examination revealed a slightly elevated bone turnover. Based on the clinical manifestations presented by our patient, kEDS was suspected. Genetic analysis revealed a novel homozygous missense mutation of PLOD1 (c.1697 G > A, p.C566Y), confirming the diagnosis of kEDS-PLOD1. The patient was treated with alfacalcidol and nifedipine. Improved physical strength and normal blood pressure were reported after 12-month follow-up. CONCLUSIONS: This is the first case of kEDS-PLOD1 of Chinese origin. We identified one novel mutation of PLOD1, extending the mutation spectrum of PLOD1. Diagnosis of kEDS-PLOD1 should be considered in patients with congenital hypotonia, progressive kyphoscoliosis, joint hypermobility, and skin hyperextensibility and confirmed by mutation analysis of PLOD1.


Asunto(s)
Síndrome de Ehlers-Danlos/genética , Cifosis/genética , Mutación Missense , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/genética , Escoliosis/genética , Adolescente , Pueblo Asiatico , Secuencia de Bases , Conservadores de la Densidad Ósea/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Síndrome de Ehlers-Danlos/tratamiento farmacológico , Síndrome de Ehlers-Danlos/etnología , Síndrome de Ehlers-Danlos/patología , Expresión Génica , Genes Recesivos , Humanos , Hidroxicolecalciferoles/uso terapéutico , Cifosis/tratamiento farmacológico , Cifosis/etnología , Cifosis/patología , Masculino , Nifedipino/uso terapéutico , Fenotipo , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/deficiencia , Escoliosis/tratamiento farmacológico , Escoliosis/etnología , Escoliosis/patología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA