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2.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542011

RESUMO

A 44-year-old woman with known trichorhinophalangeal syndrome presented with an unheralded out of hospital cardiac arrest. Transthoracic echocardiography showed severe left ventricular systolic dysfunction with an ejection fraction <25% and cardiac MRI confirmed a diagnosis of congenital non-ischaemic dilated cardiomyopathy. The case highlights a very rare syndrome, it is previously unknown association with dilated cardiomyopathy and the possible benefit of cardiac screening for patients with known trichorhinophalangeal syndrome.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Dedos/anormalidades , Doenças do Cabelo/complicações , Síndrome de Langer-Giedion/complicações , Nariz/anormalidades , Parada Cardíaca Extra-Hospitalar , Doenças Raras , Adulto , Ecocardiografia , Feminino , Doenças do Cabelo/genética , Humanos , Síndrome de Langer-Giedion/genética , Programas de Rastreamento , Fatores de Risco
3.
BMJ Case Rep ; 14(1)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509858

RESUMO

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterised by rod-cone dystrophy, obesity, postaxial polydactyly, cognitive impairment, hypogonadism, renal abnormalities, and rarely, laryngeal webs or bifid epiglottis. Most patients present with obesity. Multiple genes are involved in causation of BBS and there is also evidence of triallelic inheritance. We herein report an Asian boy who had weak cry and stridor since birth, and on evaluation was found to have both laryngeal web and bifid epiglottis. Mutation analysis revealed a homozygous variant in BBS10 gene.


Assuntos
Síndrome de Bardet-Biedl/diagnóstico , Epiglote/anormalidades , Hipotireoidismo/diagnóstico , Laringe/anormalidades , Síndrome de Bardet-Biedl/complicações , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/fisiopatologia , Broncoscopia , Chaperoninas/genética , Dedos/anormalidades , Dedos/fisiopatologia , Mutação da Fase de Leitura , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Lactente , Laringe/cirurgia , Masculino , Obesidade Pediátrica/fisiopatologia , Polidactilia/fisiopatologia , Tiroxina/uso terapêutico , Dedos do Pé/anormalidades , Dedos do Pé/fisiopatologia
4.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462008

RESUMO

We present the case of a 17-year-old Asian man diagnosed with pachydermodactyly, a rare digital fibromatosis. Although this is a non-inflammatory periarticular soft tissue disorder, the clinical appearance can mimic inflammatory arthritis. The patient had a 2-year history of fusiform swelling of multiple proximal interphalangeal joints. He was initially diagnosed with juvenile idiopathic arthritis and treated with methotrexate, but a lack of clinical response led to the diagnosis of pachydermodactyly. Recognising this rare condition can prevent unnecessary and potentially harmful treatment.


Assuntos
Artrite Juvenil/diagnóstico , Erros de Diagnóstico , Fibroma/congênito , Dedos/anormalidades , Adolescente , Diagnóstico Diferencial , Fibroma/diagnóstico , Humanos , Masculino
5.
J Clin Ultrasound ; 49(1): 62-65, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32537787

RESUMO

This report describes a variant of McKusick-Kaufman syndrome presenting with a large fetal abdominal cyst of hydrometrocolpos at 37 weeks of gestation. The diagnosis was based on the ultrasound findings of a large homogeneous hypoechoic cyst (diameter of >10 cm) with incomplete septum, thickened wall, superiorly connecting to the dilated uterus, consistent with hydrometrocolpos. Additionally, pre-axial mirror polydactyly of the left foot was suspected. Postnatal examination/work-up confirmed the prenatal findings. This is the first report of prenatal diagnosis of hydrometrocolpos with complex polydactyly of mirror image pre-axial duplications containing nine toes instead of six-toe postaxial polydactyly.


Assuntos
Anormalidades Múltiplas/diagnóstico , Dedos/anormalidades , Cardiopatias Congênitas/diagnóstico , Hidrocolpos/diagnóstico , Polidactilia/diagnóstico , Radiografia/métodos , Dedos do Pé/anormalidades , Ultrassonografia Pré-Natal/métodos , Doenças Uterinas/diagnóstico , Feminino , Feto , Humanos , Gravidez , Adulto Jovem
6.
Medicine (Baltimore) ; 99(44): e22816, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126320

RESUMO

RATIONALE: Ectrodactyly ectodermal dysplasia-cleft lip/palate (EEC) syndrome, limb-mammary syndrome (LMS), and acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome are caused by a TP63 gene disorder and have similar features. In the present article, a R319H mutation in TP63 is reported, and the correlation between genotype and phenotype is discussed based on the current case and previous literature. PATIENT CONCERNS: A 13-year-old Japanese boy had ectrodactyly in the right hand and left foot and syndactyly in the left and right foot, and tooth shape abnormalities. DIAGNOSES: Peripheral blood samples were obtained, and mutation analysis was performed. A heterozygous G>A transition at cDNA position 956 of the TP63 gene was found. The patient was diagnosed with ELA (EEC/LM/ADULT) syndrome based on his clinical features and mutation analysis results. INTERVENTIONS: The patient underwent surgery to correct the left foot malformation at 1 year of age and the right foot syndactyly at 11 years of age. OUTCOMES: No complications were observed after the first and second operations. He can walk comfortably after them, and no additional interventions will be planned in him. We continued to follow up with him up to the present. LESSONS: The concept of ELA syndrome, which is the original concept of combining 3 syndromes (EEC syndrome/LMS/ADULT syndrome) into a unique clinical entity, can help clinicians to better understand TP63-related syndromes and improve the differential diagnosis of these syndromes.


Assuntos
Anodontia/sangue , Mama/anormalidades , Fissura Palatina/sangue , Displasia Ectodérmica/sangue , Dedos/anormalidades , Deformidades Congênitas da Mão/sangue , Obstrução dos Ductos Lacrimais/sangue , Deformidades Congênitas dos Membros/sangue , Unhas Malformadas/sangue , Transtornos da Pigmentação/sangue , Fatores de Transcrição/análise , Proteínas Supressoras de Tumor/análise , Adolescente , Anodontia/genética , Fissura Palatina/genética , Displasia Ectodérmica/genética , Deformidades Congênitas da Mão/genética , Humanos , Japão , Obstrução dos Ductos Lacrimais/genética , Deformidades Congênitas dos Membros/genética , Masculino , Mutação/genética , Unhas Malformadas/genética , Transtornos da Pigmentação/genética , Fatores de Transcrição/sangue , Proteínas Supressoras de Tumor/sangue
8.
BMC Med Genet ; 21(1): 158, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746809

RESUMO

BACKGROUND: Okur-Chung neurodevelopmental syndrome (OCNDS) and tricho-rhino-phalangeal syndrome type I (TRPSI) are rare Mendelian diseases. OCNDS is caused by CSNK2A1 gene variants and TRPSI is caused by the TRPS1gene. However, to have two Mendelian diseases in one patient is even rarer. CASE PRESENTATION: A 6-year-10-month-old boy characterized by special facial features, short stature and mental retardation was referred to our pediatric endocrinology department. Whole-exome sequencing (WES) was done to detect the molecular basis of his disease. This patient was confirmed to carry two variants in the CSNK2A1 gene and one in the TRPS1 gene. The variant in the CSNK2A1 gene was vertically transmitted from his father, and the variant in TRPS1 gene from his mother. These two variants are classified as pathogenic and the causes of the presentation in this child. This patient's father and mother have subsequently been diagnosed as having OCNDS and TRPSI respectively. CONCLUSION: This is the first reported case of a dual molecular diagnosis of tricho-rhino-phalangeal syndrome type I and Okur-Chung neurodevelopmental syndrome in the same patient. This patient is the first published example of vertical transmission of this recurrent CSN2A1 variant from parent to child. A novel variant in the TRPS1 gene that is pathogenic was also identified. In conclusion, identification of the variants in this patient expands the phenotypes and molecular basis of dual Mendelian diseases.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Dedos/anormalidades , Doenças do Cabelo/genética , Síndrome de Langer-Giedion/genética , Transtornos do Neurodesenvolvimento/genética , Nariz/anormalidades , Sequência de Bases , Criança , Feminino , Humanos , Masculino , Linhagem
9.
BMC Med Genet ; 21(1): 140, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32605629

RESUMO

BACKGROUND: Cohen syndrome, an autosomal recessive syndrome, is a rare syndrome with diverse clinical manifestations including failure to thrive, hypotonia, hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, neutropenia and a friendly character. It is associated with mutations of the vacuolar protein sorting 13 homolog B (VPS13B) gene, which is involved in the development of the ocular, hematological and central nervous systems. This gene encodes a transmembrane protein playing a crucial role in preserving the integrity of the Golgi complex. To date, more than 150 mutations of VPS13B have been reported in over 200 Cohen syndrome patients. Missense or nonsense mutations are the most common mutations. CASE PRESENTATION: A 4-year-old girl, born to consanguineous parents, was referred to the pediatric clinical immunology outpatient clinic for investigation of recurrent neutropenia with a history of recurrent infections in the past year. On physical examination, she had the characteristic facial features of Cohen syndrome, developmental delay and speech disorder. She had a cheerful disposition, and her mother gave a history of feeding difficulties in her first months of life. She did not present any ophthalmologic or cardiac abnormalities. Her lab results revealed moderate neutropenia. Serum IgG, IgM, IgA and IgE levels were normal. She fulfilled the clinical diagnostic criteria for Cohen syndrome. WES revealed a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49). Currently, she is not experiencing any severe problem, and she undergoes irregular medical treatment once her neutrophil count decreases under the normal limit. Her verbal and motor abilities have improved as a result of speech and occupational therapies. CONCLUSION: We reported a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49) in a 4-year-old girl with Cohen syndrome. Cohen syndrome should be considered in differential diagnosis of any child with intellectual disability and neutropenia.


Assuntos
Dedos/anormalidades , Deficiência Intelectual/genética , Microcefalia/genética , Hipotonia Muscular/genética , Mutação/genética , Miopia/genética , Obesidade/genética , Degeneração Retiniana/genética , Proteínas de Transporte Vesicular/genética , Pré-Escolar , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Fenótipo
10.
BMC Med Genet ; 21(1): 126, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513120

RESUMO

BACKGROUND: Nakajo-Nishimura syndrome (NNS) is an autosomal recessive heredity disorder, one of a spectrum of autoinflammatory diseases named proteasome-associated autoinflammatory syndrome (PRAAS) caused by mutations of PSMB8 gene. NNS is characterized by pernio-like skin rashes, intermittent fever, and long clubbed fingers and toes with joint contractures, partially with progressive lipomuscular atrophy, emaciation, hepatosplenomegaly and basal ganglion calcification. CASE PRESENTATION: We presented a sporadic case of NNS with compound heterozygous mutations in the PSMB8 gene. The 4-year-old boy was affected by progressive erythematous plaques on his nose and gradually involved hands and feet later with characteristic appearance of long clubbed fingers. The repetitive periodic intermittent fever was recorded. By gene sequencing, novel compound heterozygous mutations c.373C > T (p.R125C) and c.355G > A (p.D119N) in the PSMB8 gene were found. The patient responded well to low dosage of oral methylprednisolone. CONCLUSIONS: We reported novel compound heterozygous mutations in PSMB8 in a sporadic Chinese NNS patient.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Eritema Nodoso/genética , Dedos/anormalidades , Mutação/genética , Complexo de Endopeptidases do Proteassoma/genética , Sequência de Bases , Pré-Escolar , Eritema Nodoso/patologia , Dedos/patologia , Heterozigoto , Humanos , Masculino
11.
Exp Mol Pathol ; 115: 104471, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32446860

RESUMO

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a developmental brain disorder characterized by an enlarged brain size with bilateral perisylvian polymicrogyria and a variable degree of ventriculomegaly. MPPH syndrome is associated with oromotor dysfunction, epilepsy, intellectual disability and postaxial hexadactyly. The molecular diagnosis of this disorder is established by the identification of a pathogenic variant in either AKT3, CCND2 or PIK3R2. Previously reported AKT3 variants are associated with various brain abnormalities and may lead to megalencephaly. MPPH syndrome is usually due to germline pathogenic AKT3 variants. Somatic mosaic pathogenic variants associated with hemimegalencephaly, which is similar to MPPH, have also been observed. A Hungarian Roma family with two half-siblings, which present with intellectual disability, dysmorphic features, epilepsy, brain malformations, and megalencephaly was studied. Whole exome sequencing (WES) analysis was performed. WES analysis revealed a heterozygous c.1393C > T p.(Arg465Trp) pathogenic missense AKT3 variant in both affected half-siblings. The variant was verified via Sanger sequencing and was not present in the DNA sample from the healthy mother, which was derived from peripheral blood, suggesting maternal germline mosaicism. In conclusion, this is the first report in which maternal germline mosaicism of a rare pathogenic AKT3 variant leads to autosomal dominantly inherited MPPH syndrome.


Assuntos
Dedos/anormalidades , Células Germinativas/metabolismo , Hidrocefalia/congênito , Padrões de Herança/genética , Megalencefalia/genética , Mosaicismo , Polidactilia/genética , Polimicrogiria/genética , Proteínas Proto-Oncogênicas c-akt/genética , Dedos do Pé/anormalidades , Adolescente , Criança , Feminino , Dedos/diagnóstico por imagem , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/genética , Imagem por Ressonância Magnética , Masculino , Megalencefalia/diagnóstico por imagem , Linhagem , Fenótipo , Polidactilia/diagnóstico por imagem , Polimicrogiria/diagnóstico por imagem , Irmãos , Síndrome , Dedos do Pé/diagnóstico por imagem
12.
Plast Reconstr Surg ; 145(5): 1215-1221, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32332541

RESUMO

BACKGROUND: There is scant literature regarding patient-reported outcomes after reconstruction for congenital hand syndactyly. Understanding patient perceptions of the postoperative outcome may facilitate a more evidence-based discussion of expectations after reconstruction. METHODS: All patients undergoing congenital syndactyly reconstruction at Ann and Robert H. Lurie Children's Hospital of Chicago between January of 2007 and December of 2015 were identified. Patient-Reported Outcomes Measurement Information System questionnaires were completed by patients; parent-proxy questionnaires were completed for patients 10 years of age and younger and those unable to complete the questionnaire independently. A retrospective chart review was also performed to capture demographic and clinical information. RESULTS: The authors identified 124 patients meeting inclusion criteria; 51 completed the Patient-Reported Outcomes Measurement Information System surveys (response rate, 41.1 percent). The survey score for upper extremity function was 41.8 ± 11. Upper extremity function was further impaired in patients with a documented history of developmental delay (23.8 ± 6.2 versus 44.2 ± 10.2). Parents completing surveys on behalf of their children reported higher pain interference scores than self-responders. CONCLUSIONS: The Patient-Reported Outcomes Measurement Information System is a valuable tool for measuring patient-reported outcomes in patients with syndactyly. Patients who have undergone reconstruction for syndactyly experience minor impairments in upper extremity function, but other aspects of their health-related quality of life are comparable to those of the general population. Developmental delay may be associated with additional impairments in upper extremity function and should be discussed when considering surgical reconstruction.


Assuntos
Dedos/anormalidades , Procedimentos Ortopédicos/efeitos adversos , Dor Pós-Operatória/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Sindactilia/cirurgia , Fatores Etários , Chicago , Criança , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Dedos/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/psicologia , Qualidade de Vida , Recuperação de Função Fisiológica , Estudos Retrospectivos , Autorrelato/estatística & dados numéricos , Sindactilia/complicações , Sindactilia/fisiopatologia , Resultado do Tratamento , Extremidade Superior/fisiopatologia
13.
J Hand Surg Asian Pac Vol ; 25(2): 236-239, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32312213

RESUMO

We describe a case of an adult patient presenting with cubital tunnel syndrome in the setting of previously undiagnosed macrodactyly. Early diagnosis and management of macrodactyly is important to help prevent symptoms associated with compromised peripheral nerves and reduce the likelihood of the permanent motor and sensory sequelae of prolonged nerve compression.


Assuntos
Síndrome do Túnel Ulnar/diagnóstico , Dedos/anormalidades , Deformidades Congênitas dos Membros/complicações , Síndrome do Túnel Ulnar/etiologia , Articulação do Cotovelo/fisiologia , Feminino , Humanos , Deformidades Congênitas dos Membros/diagnóstico , Pessoa de Meia-Idade
15.
J Hand Surg Asian Pac Vol ; 25(1): 1-12, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32000609

RESUMO

Background: Different techniques are used to release simple and complex congenital syndactyly in order to create an adequate web space, and to separate the fingers to allow independent function. Methods: This article is a systematic review of the literature, aiming to evaluate the evidence for the different techniques and outcome measures utilised. Results: The studies consisted mainly of retrospective, non-controlled descriptive series and a few retrospective cohort studies. The level of evidence is predominantly poor. Conclusions: Although recommendations in favour of any particular surgical technique cannot be given based on evidence, a number of conclusions can be drawn out of the existing literature with regards to the design of the incisions for finger separation, use of pulp flaps and grafts.


Assuntos
Dedos/anormalidades , Dedos/cirurgia , Sindactilia/cirurgia , Humanos , Procedimentos Ortopédicos , Retalhos Cirúrgicos
16.
Invest Ophthalmol Vis Sci ; 61(2): 29, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32084271

RESUMO

Purpose: Cone-rod dystrophy (CRD) is a rare hereditary eye disorder that causes progressive degeneration of cone and rod photoreceptors. More than 30 genes, including RAB28, have been associated with CRD; however, only a few RAB28 variants have been reported to be associated with CRD. In this study, we describe two brothers with CRD and a homozygous missense variant, c.55G>A (p.Gly19Arg), in RAB28. Methods: The missense variant was identified as part of a study investigating underlying genetic defects in a large patient cohort (n = 667) using targeted next-generation sequencing of 125 genes associated with retinal dystrophy. Cellular localization of RAB28 and ciliogenesis in patient fibroblasts were investigated by immunofluorescence microscopy. The effect of the missense variant on RAB28 expression level was investigated by quantitative real-time PCR. Results: Two brothers of a consanguineous couple presented with CRD, postaxial polydactyly (PAP), and myopia. Both brothers had a homozygous missense RAB28 variant located in the G1 box of the guanosine triphosphate/guanosine diphosphate binding domain of RAB28. This missense variant caused a considerable reduction of RAB28 localized to the cilia, whereas ciliogenesis seemed unaffected. Conclusions: The missense variant in RAB28 is classified as likely pathogenic with functional effect on protein localization. The combination of retinal dystrophy and PAP are well known from ciliopathies; however, more data are needed to finally conclude that the RAB28 variant described here is the cause of PAP in these brothers.


Assuntos
Cílios/metabolismo , Distrofias de Cones e Bastonetes/genética , Dedos/anormalidades , Mutação de Sentido Incorreto , Polidactilia/genética , Dedos do Pé/anormalidades , Proteínas rab de Ligação ao GTP , Criança , Humanos , Masculino , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
18.
Curr Opin Pediatr ; 32(1): 120-124, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31851054

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to describe various forms of hand polydactyly and their different treatment approaches. Hand polydactyly is commonly classified as ulnar (small finger) or radial (thumb). Polydactyly can be sporadic, genetic, and/or associated with syndromic conditions. RECENT FINDINGS: Both ulnar and radial polydactyly can be surgically treated to optimize hand aesthetics and function. Timing of surgery is based on multiple factors, most notably including safety of anesthesia and socialization of the affected child. The pediatrician should be aware of potential associated conditions, such as chondroectodermal dysplasia or Ellis-van Creveld syndrome for ulnar polydactyly. SUMMARY: Polydactyly is a common congenital hand difference and can be broadly be classified by radial or ulnar involvement. Polydactyly warrants hand surgical referral, as surgical treatment is often indicated. Pediatricians should be aware of treatment options, as well as of commonly associated anomalies and syndromes.


Assuntos
Dedos/anormalidades , Polidactilia/cirurgia , Criança , Dedos/cirurgia , Deformidades Congênitas da Mão/classificação , Deformidades Congênitas da Mão/epidemiologia , Deformidades Congênitas da Mão/cirurgia , Humanos , Polidactilia/classificação , Polidactilia/epidemiologia , Polegar/anormalidades , Polegar/cirurgia
19.
Rehabil Nurs ; 45(2): 106-113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30192341

RESUMO

PURPOSE: This study aimed to determine the effectiveness of olive oil in controlling morning inflammatory pain of phalanges and knees among women with rheumatoid arthritis. DESIGN: This is a randomized clinical trial, which was done in Arak, Iran. METHOD: After selecting 60 women based on a convenience sampling method, they were randomly allocated into five groups. A demographic questionnaire, the Visual Analogue Scale, and the Disease Activity Score 28 were completed. After 12 weeks of interventions, the last two scales were again completed. All data were analyzed using t test, Kruskal-Wallis test, and Friedman test. RESULTS: The mean age of the women was 40 ± 10.5 years. The result of the Friedman test showed a significant difference (p ≤ .001) among the total mean of groups before and after interventions. The post hoc test (least significant difference [LSD]) showed a significant difference (p ≤ .001) between the mean of Disease Activity Score 28 in the group using olive oil for massaging. Results also showed that there are significant differences (p ≤ .001) among the mean of Visual Analogue Scale rates, among the mean of the number of painful joints, and among the mean of the number of swollen joints after intervention in the five groups. CONCLUSION: Applying topical extra virgin olive oil, Piroxicam gel, and paraffin oil; dry massaging; and taking routine drugs alone were all effective in controlling rheumatic arthritis manifestations, respectively. Therefore, applying topical extra virgin olive oil for controlling of inflammatory pain of joints in rheumatic arthritis is recommended. CLINICAL RELEVANCE: In comparison with other medical ointments for RA, olive oil has lower expenditure and is findable in many homes.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Dedos/anormalidades , Joelho/anormalidades , Azeite de Oliva/uso terapêutico , Adulto , Artrite Reumatoide/fisiopatologia , Feminino , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Azeite de Oliva/farmacologia , Manejo da Dor/métodos , Manejo da Dor/normas , Manejo da Dor/estatística & dados numéricos , Estatísticas não Paramétricas
20.
Eur J Med Genet ; 63(1): 103610, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30602132

RESUMO

Cohen syndrome is an autosomal recessive disease characterized by myopia, retinal dystrophy, neutropenia, short stature, microcephaly, persistent hypotonia, intellectual disability (ID), and a distinct facial appearance. Cohen syndrome is caused by mutations, such as single nucleotide variants (SNVs) and small insertions/deletions, and copy number variations (CNVs) in vacuolar protein sorting 13 homolog B (VPS13B). Here, we report Japanese siblings with ID, who were subsequently diagnosed with Cohen syndrome by whole exome sequencing (WES). The older sister had hypotonia and mild to moderate ID. The younger sister had short stature, postnatal onset microcephaly, and developmental delay. No pathogenic mutations, including SNVs or small insertions/deletions, were found by WES. Comparative genomic hybridization (CGH)-array did not detect pathogenic copy-number variations. However, using log2-ratio values calculated from WES depth data, we detected pathogenic biallelic heterozygous CNVs in VPS13B in both sisters: a maternally-derived exons 8-15 deletion and a paternally-derived exons 32-33 deletion. Interestingly, the sisters did not show obvious clinical features suggestive of Cohen syndrome, including the distinct facial appearance. These results support the idea that the typical facial features of Cohen syndrome do not appear in early childhood, and that the late appearance of distinctive clinical features results in delayed diagnosis. Furthermore, these results show the possibility that CNV analysis using log2-ratio values calculated from WES depth data is a useful and effective method to detect CNVs, such as the deletion of multiple exons.


Assuntos
Dedos/anormalidades , Predisposição Genética para Doença , Deficiência Intelectual/genética , Microcefalia/genética , Hipotonia Muscular/genética , Miopia/genética , Obesidade/genética , Degeneração Retiniana/genética , Proteínas de Transporte Vesicular/genética , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA/genética , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Exoma/genética , Feminino , Dedos/patologia , Heterozigoto , Humanos , Deficiência Intelectual/patologia , Masculino , Microcefalia/patologia , Hipotonia Muscular/patologia , Mutação/genética , Miopia/patologia , Obesidade/patologia , Linhagem , Fenótipo , Degeneração Retiniana/patologia , Irmãos , Sequenciamento Completo do Exoma/métodos
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