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1.
Nat Commun ; 15(1): 2229, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472182

RESUMO

Apoptosis occurs during development when a separation of tissues is needed. Synovial joint formation is initiated at the presumptive site (interzone) within a cartilage anlagen, with changes in cellular differentiation leading to cavitation and tissue separation. Apoptosis has been detected in phalangeal joints during development, but its role and regulation have not been defined. Here, we use a mouse model of brachydactyly type A1 (BDA1) with an IhhE95K mutation, to show that a missing middle phalangeal bone is due to the failure of the developing joint to cavitate, associated with reduced apoptosis, and a joint is not formed. We showed an intricate relationship between IHH and interacting partners, CDON and GAS1, in the interzone that regulates apoptosis. We propose a model in which CDON/GAS1 may act as dependence receptors in this context. Normally, the IHH level is low at the center of the interzone, enabling the "ligand-free" CDON/GAS1 to activate cell death for cavitation. In BDA1, a high concentration of IHH suppresses apoptosis. Our findings provided new insights into the role of IHH and CDON in joint formation, with relevance to hedgehog signaling in developmental biology and diseases.


Assuntos
Braquidactilia , Proteínas Hedgehog , Camundongos , Animais , Proteínas Hedgehog/metabolismo , Braquidactilia/genética , Braquidactilia/metabolismo , Articulações/metabolismo , Apoptose
2.
Mol Genet Genomic Med ; 12(2): e2393, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38407575

RESUMO

BACKGROUND: Brachydactyly type E (BDE) is a general term characterized by variable shortening of metacarpals and metatarsals, with phalanges affected frequently. It can occur as an isolated form or part of syndromes and manifest a high degree of phenotypic variability. In this study, we have identified the clinical characteristics and pathogenic causes of a four-generation pedigree with 10 members affected by BDE and short stature. METHODS: After the informed consent was signed, clinical data and peripheral blood samples were collected from available family members. Karyotype analysis, array-CGH, next-generation sequencing, and Sanger sequencing were employed to identity the pathogenic candidate gene. RESULTS: No translocation or microdeletion/duplication was found in karyotype analysis and array-CGH; hence, a novel heterozygous mutation, c.146dupA. p.S50Vfs*22, was detected by next-generation sequencing in PTHLH gene, leading to a premature stop codon. Subsequently, the mutation was confirmed by Sanger sequencing and co-segregation analysis. CONCLUSION: In this study, we described a novel heterozygous mutation (c.146dupA. p.S50Vfs*22) of gene PTHLH in a Chinese family. The mutation could induce a premature stop codon leading to a truncation of the protein. Our study broadened the mutation spectrum of PTHLH in BDE.


Assuntos
Braquidactilia , Nanismo , Humanos , Braquidactilia/genética , Códon sem Sentido , Mutação , Proteína Relacionada ao Hormônio Paratireóideo/genética
3.
Life Sci Alliance ; 7(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38331475

RESUMO

Brachydactyly type E (BDE), shortened metacarpals, metatarsals, cone-shaped epiphyses, and short stature commonly occurs as a sole phenotype. Parathyroid hormone-like protein (PTHrP) has been shown to be responsible in all forms to date, either directly or indirectly. We used linkage and then whole genome sequencing in a small pedigree, to elucidate BDE and identified a truncated disintegrin-and-metalloproteinase-19 (ADAM19) allele in all affected family members, but not in nonaffected persons. Since we had shown earlier that the extracellular domain of the parathyroid hormone receptor (PTHR1) is subject to an unidentified metalloproteinase cleavage, we tested the hypothesis that ADAM19 is a sheddase for PTHR1. WT ADAM19 cleaved PTHR1, while mutated ADAM-19 did not. We mapped the cleavage site that we verified with mass spectrometry between amino acids 64-65. ADAM-19 cleavage increased Gq and decreased Gs activation. Moreover, perturbed PTHR1 cleavage by ADAM19 increased ß-arrestin2 recruitment, while cAMP accumulation was not altered. We suggest that ADAM19 serves as a regulatory element for PTHR1 and could be responsible for BDE. This sheddase may affect other PTHrP or PTH-related functions.


Assuntos
Braquidactilia , Proteína Relacionada ao Hormônio Paratireóideo , Humanos , Proteína Relacionada ao Hormônio Paratireóideo/genética , Braquidactilia/genética , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Metaloproteases , Proteínas ADAM
4.
J Clin Hypertens (Greenwich) ; 26(3): 295-298, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38319596

RESUMO

The authors describe the case of a 16-year-old male who was incidentally found to have a blood pressure of 200/? mmHg 6 months previously due to blurred vision and was diagnosed with "high risk of hypertension grade 3, renal insufficiency, hypertensive encephalopathy, hypertensive heart disease, and fundus hemorrhage" after relevant examinations were performed. His blood pressure fluctuated around 120/90 mmHg after beginning antihypertensive treatment. While the diagnostic work-up of his hypertension was inconclusive, he had severe hypertension with brachydactyly type E and short stature on physical examination. The patient's cardiac damage and renal insufficiency ultimately returned to normal after strict blood pressure control, suggesting that hypertension and brachydactyly syndrome alone do not cause cardiac and renal damage.


Assuntos
Braquidactilia , Hipertensão , Insuficiência Renal , Masculino , Humanos , Adolescente , Hipertensão/tratamento farmacológico , Hipertensão/diagnóstico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Braquidactilia/diagnóstico , Braquidactilia/tratamento farmacológico
5.
Clin Genet ; 105(4): 434-439, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38108099

RESUMO

Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) is an ultra-rare skeletal dysplasia caused by heterozygous intragenic RUNX2 duplications, comprising either exons 3 to 5 or exons 3 to 6 of RUNX2. In this study, we describe a 14-year-old Belgian boy with metaphyseal dysplasia with maxillary hypoplasia but without brachydactyly. Clinical and radiographic examination revealed mild facial dysmorphism, dental anomalies, enlarged clavicles, genua valga and metaphyseal flaring and thin cortices with an osteoporotic skeletal appearance. Exome sequencing led to the identification of a de novo heterozygous tandem duplication within RUNX2, encompassing exons 3 to 7. This duplication is larger than the ones previously reported in MDMHB cases since it extends into the C-terminal activation domain of RUNX2. We review previously reported cases with MDMHB and highlight the resemblance of this disorder with Pyle disease, which may be explained by intersecting molecular pathways between RUNX2 and sFRP4. This study expands our knowledge on the genotypic and phenotypic characteristics of MDMHB and the role of RUNX2 in rare bone disorders.


Assuntos
Braquidactilia , Displasia Cleidocraniana , Micrognatismo , Osteocondrodisplasias , Masculino , Humanos , Adolescente , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Proteínas Proto-Oncogênicas
6.
JBJS Case Connect ; 13(4)2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37797171

RESUMO

CASE: A 5-year-old boy presented with multiple bony swellings in the dorsal spine region, restricted left shoulder movement, and a previous misdiagnosis of hereditary multiple exostoses (HMEs) resulting in unnecessary excision of the right scapular lesion. Clinical examination revealed hallux valgus, brachydactyly, and limited neck movement. Radiography and computed tomography confirmed a diagnosis of fibrodysplasia ossificans progressiva (FOP). CONCLUSION: This case report underscores the importance of accurate diagnosis and differentiation between FOP and HME. Hallux valgus, brachydactyly, and restricted neck movement suggested FOP. It is paramount for orthopaedic surgeons to exclude rare disorders before performing any interventions. Biopsies or resections of bone formation areas should be avoided for patients with FOP.


Assuntos
Braquidactilia , Hallux Valgus , Miosite Ossificante , Masculino , Humanos , Pré-Escolar , Miosite Ossificante/diagnóstico por imagem , Radiografia , Tomografia Computadorizada por Raios X
7.
Genes (Basel) ; 14(2)2023 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-36833393

RESUMO

2q37 microdeletion/deletion syndrome (2q37DS) is one of the most common subtelomeric deletion disorders, caused by a 2q37 deletion of variable size. The syndrome is characterized by a broad and diverse spectrum of clinical findings: characteristic facial dysmorphism, developmental delay/intellectual disability (ID), brachydactyly type E, short stature, obesity, hypotonia in infancy, and abnormal behavior with autism spectrum disorder. Although numerous cases have been described so far, the exact mapping of the genotype and phenotype have not yet been achieved. MATERIALS AND METHODS: In this study we analyzed nine newly diagnosed cases with 2q37 deletion (3 male/6 female, aged between 2 and 30 years old), and followed up at the Iasi Regional Medical Genetics Centre. All patients were tested first with MLPA using combined kits P036/P070 subtelomeric screening mix and follow-up mix P264; after, the deletion size and location were confirmed via CGH-array. We compared our findings with the data of other cases reported in the literature. RESULTS: From nine cases, four had pure 2q37 deletions of variable sizes, and five presented deletion/duplication rearrangements (with chromosomes 2q, 9q, and 11p). In most cases, characteristic phenotypic aspects were observed: 9/9 facial dysmorphism, 8/9 global developmental delay and ID, 6/9 hypotonia, 5/9 behavior disorders, and 8/9 skeletal anomalies-especially brachydactyly type E. Two cases had obesity, one case had craniosynostosis, and four had heart defects. Other features found in our cases included translucent skin and telangiectasias (6/9), and a hump of fat on the upper thorax (5/9). CONCLUSIONS: Our study enriches the literature data by describing new clinical features associated with 2q37 deletion, and possible genotype-phenotype correlations.


Assuntos
Transtorno do Espectro Autista , Braquidactilia , Deficiência Intelectual , Humanos , Masculino , Feminino , Braquidactilia/diagnóstico , Braquidactilia/genética , Hipotonia Muscular , Estudos de Associação Genética , Deficiência Intelectual/genética , Obesidade
8.
Am J Med Genet A ; 191(1): 64-69, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36208065

RESUMO

ERI1 is an evolutionary conserved 3'-5' exonuclease with an important function in multiple RNA processing pathways. Although the molecular mechanisms in which ERI1 is involved have been studied extensively in model organisms, the pathology associated with ERI1 variants in humans has remained elusive because no case has been reported so far. Here, we present a case of a female patient with a homozygous nonsense variant in ERI1 gene. The patient exhibits mild intellectual disability, eyelid ptosis, and anomalies in her hands and feet (brachydactyly, clinodactyly, dysplastic/short nail of halluces, brachytelephalangy, short metacarpals, and toe syndactyly). This case report is the first of its kind and is invaluable for understanding ERI1 pathology in humans.


Assuntos
Braquidactilia , Deficiência Intelectual , Deformidades Congênitas dos Membros , Sindactilia , Humanos , Feminino , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/genética , Sindactilia/diagnóstico , Sindactilia/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Síndrome , Exorribonucleases/genética
9.
Genet Med ; 25(1): 135-142, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399134

RESUMO

PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder. METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature. RESULTS: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss. CONCLUSION: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities.


Assuntos
Braquidactilia , Nanismo , Deficiência Intelectual , Anormalidades Musculoesqueléticas , Transtornos do Neurodesenvolvimento , Humanos , Transtornos do Neurodesenvolvimento/genética , Deficiência Intelectual/genética , Nanismo/genética , Obesidade/genética , Fenótipo , Proteína-Arginina N-Metiltransferases/genética
10.
Clin Genet ; 103(5): 574-579, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36504352

RESUMO

Acromesomelic dysplasias (AMD) are a group of skeletal dysplasia characterized by shortening of the middle and distal segments of the limbs. Recently, biallelic PRKG2 variants have been reported to cause a new type of AMD. We detected biallelic novel variant (c.1635-1G > C) in PRKG2 in two brothers with mild to severe short stature, short limbs, cubitus varus, and brachydactyly. Radiological examination showed platyspondyly with anterior beaking of the vertebral bodies, stubby long bones with metaphyseal flaring and moderate brachydactyly with cone-shaped epiphyses of the middle and proximal phalanges. Upper limb proportions of the older brother were clinically classified as rhizomelic, however radiologic findings supported acromesomelia, along with the elbow limitation. Annual follow-ups of the older brother from the age of 5 to 20 years revealed progression of short stature with age but platyspondyly and anterior beaking became less conspicuous. The younger brother showed milder short stature and less conspicuous disproportion of the limbs than those of the older brother; however, platyspondyly and anterior beaking were more prominent on the radiographs obtained at the same age. In conclusion, this report provides new insights into the natural history of AMD type PRKG2 confirming the intrafamilial heterogeneity.


Assuntos
Braquidactilia , Osteocondrodisplasias , Adolescente , Criança , Pré-Escolar , Humanos , Masculino , Adulto Jovem , Proteína Quinase Dependente de GMP Cíclico Tipo II , Osteocondrodisplasias/diagnóstico , Irmãos , Extremidade Superior
11.
Cytogenet Genome Res ; 162(5): 237-243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36516793

RESUMO

Brachydactyly mental retardation syndrome (BDMR) typically results from large deletions (>2-9 Mb) in distal 2q37. Haploinsufficiency of HDAC4 with incomplete penetrance has been proposed as the primary genetic cause of BDMR. To date, pure 2q37 deletions distal to HDAC4 were reported only in a limited number of individuals who share a subset of the clinical manifestations seen in cases with 2q37 deletions encompassing HDAC4. Here, we present a 4-year-old African American male who carries the smallest established 2q37.3 deletion distal to HDAC4 (827.1 kb; 16 OMIM genes). His clinical features that overlap with BDMR phenotypes include expressive-receptive language delay, behavioral issues, mild facial dysmorphism such as frontal bossing, and bilateral 5th finger brachydactyly and clinodactyly. The deletion was inherited from his mother with a history of learning difficulties and similar facial dysmorphism. This case provides important genotype-phenotype correlation information and suggests a 2q37 region distal to HDAC4 encompassing the HDLBP gene may contribute to a subset of clinical features overlapping with those seen in individuals with BDMR.


Assuntos
Braquidactilia , Deficiência Intelectual , Masculino , Humanos , Deficiência Intelectual/genética , Braquidactilia/genética , Deleção Cromossômica , Estudos de Associação Genética , Fenótipo , Cromossomos Humanos Par 2
12.
BMC Pediatr ; 22(1): 528, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064339

RESUMO

BACKGROUND: Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type B1 (BDB1) and brachydactyly type B2 (BDB2). BDB1 is the most severe form of brachydactyly and is caused by truncating variants in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene. CASE PRESENTATION: Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein. CONCLUSION: The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.


Assuntos
Braquidactilia , Sindactilia , Braquidactilia/diagnóstico , Braquidactilia/genética , Ossos do Carpo/anormalidades , Feminino , Deformidades Congênitas do Pé , Deformidades Congênitas da Mão , Humanos , Linhagem , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Estribo/anormalidades , Sinostose , Ossos do Tarso/anormalidades
13.
Am J Med Genet A ; 188(10): 2969-2975, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35852485

RESUMO

ERF-related craniosynostosis syndrome type 4 (CRS4, OMIM #600775) is a rare autosomal dominant malformation syndrome, caused by pathogenic variants in the ERF gene and characterized by craniosynostosis, developmental delay, and dysmorphic features such as hypertelorism, exophthalmos, depressed nasal bridge, and retrognathia. So far, there are mostly individual reports and only a few descriptions of families with more than two affected patients, allowing statements about the penetrance of a certain variant and its variability only to a limited extent. In this study, we report an in-depth analysis of the clinical course of six family members from three generations with the novel heterozygous nonsense variant c.286A>T (p.Lys96*) in the ERF gene. At the time of examination, all of the six patients showed mild dysmorphic features and brachydactyly, five were overweight/obese and had delayed speech development, and four were short in stature. Hyperactivity, a short concentration span and a history of learning difficulties were found in half of the affected family members. To this day, none of the patients developed increased intracranial hypertension that would require surgical intervention. This work provides further information on the expressive variability of an ERF variant in six members of one family and focuses on the need for close neuropediatric surveillance.


Assuntos
Artrogripose , Braquidactilia , Craniossinostoses , Braquidactilia/genética , Craniossinostoses/diagnóstico , Craniossinostoses/genética , Craniossinostoses/patologia , Família , Heterozigoto , Humanos , Proteínas Repressoras/genética
14.
Mol Genet Genomics ; 297(5): 1195-1214, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35907958

RESUMO

Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited abnormalities of human appendicular skeleton. The bones of appendicular skeleton have central role in locomotion and movement. The different types of appendicular skeletal abnormalities are well described in the report of "Nosology and Classification of Genetic skeletal disorders: 2019 Revision". In the current article, we intend to present the embryology, developmental pathways, disorders and the molecular genetics of the appendicular skeletal malformations. We mainly focused on the polydactyly, syndactyly, brachydactyly, split-hand-foot malformation and clubfoot disorders. To our knowledge, only nine genes of polydactyly, five genes of split-hand-foot malformation, nine genes for syndactyly, eight genes for brachydactyly and only single gene for clubfoot have been identified to be involved in disease pathophysiology. The current molecular genetic data will help life sciences researchers working on the rare skeletal disorders. Moreover, the aim of present systematic review is to gather the published knowledge on molecular genetics of appendicular skeleton, which would help in genetic counseling and molecular diagnosis.


Assuntos
Deformidades Congênitas dos Membros , Braquidactilia/enzimologia , Braquidactilia/genética , Pé Torto Equinovaro/embriologia , Pé Torto Equinovaro/genética , Humanos , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/embriologia , Deformidades Congênitas dos Membros/genética , Biologia Molecular , Polidactilia/embriologia , Polidactilia/genética , Sindactilia/embriologia , Sindactilia/genética
15.
Orthop Surg ; 14(9): 2386-2390, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35819086

RESUMO

Brachydactyly is a common feature of congenital hand anomalies characterized by shortening of the phalanges and/or metacarpals. Mutation of growth differentiation factor-5 (GDF5) may result in loss of appearance and function in brachydactyly type C (BDC). Herein, we describe an 11 year-old Chinese BDC patient with significant shortening of the 1st, 2nd, 3rd, and 5th digits. Notably, according to the analysis of metacarpophalangeal pattern profiles, we do not think the 4th digit appears unaffected as usual. In this patient a novel heterozygous frameshift mutation was identified (c.349delG) causing termination of translation after translating six amino acids from codon 117 (p.A117fs*6). This mutation is located in the propeptide region of GDF5, causing GDF5 haploinsufficiency in BDC. Considering our results expanding the genetic spectrum of BDC-causing mutations, further molecular analysis to diagnose and reclassify isolated brachydactyly on the basis of genotype rather than phenotype is warranted.


Assuntos
Braquidactilia , Ossos Metacarpais , Aminoácidos/genética , Braquidactilia/diagnóstico , Braquidactilia/genética , China , Mutação da Fase de Leitura , Humanos , Ossos Metacarpais/diagnóstico por imagem , Mutação
17.
J Hand Surg Eur Vol ; 47(10): 1032-1038, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35722929

RESUMO

Brachydactyly Type D is a congenital condition of the thumb in which there is a short and broad thumbnail. Although the thumb function is often unaffected, some patients seek surgery for cosmetic improvement. This study aimed to describe our method of distraction lengthening to correct nail deformity in brachydactyly Type D. A total of 163 thumbs in 95 patients underwent this surgery between 2018 and 2021.The mean thumbnail length improved from 9 mm to 15 mm, with a mean percentage increase of 62%. The ratio of nail length to width changed from 0.6 to 1.1, which was equal to normal. The mean increased fingernail length/width ratio was 0.5, with a percentage change of 78%. No obvious surgical scar was observed. The thumb function was not significantly affected. We conclude that aesthetic correction of short nail deformity in brachydactyly Type D can be achieved by distraction lengthening with high satisfaction and without functional impairment.Level of evidence: IV.


Assuntos
Braquidactilia , Doenças da Unha , Unhas Malformadas , Osteogênese por Distração , Humanos , Osteogênese por Distração/métodos , Braquidactilia/cirurgia , Resultado do Tratamento , Unhas Malformadas/cirurgia , Estética
18.
Ann Plast Surg ; 89(1): 42-48, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35502951

RESUMO

BACKGROUND: Brachydactyly (BD) type C is a rare form of familial BD caused by GDF5 mutations. Some of the affected children have severe clinodactyly requiring surgery. The literature is limited to case reports. PATIENTS AND METHODS: The current retrospective study included 15 Saudi Arabian families with 42 affected children seen by the author for 25 years. A total of 23 digits (in 23 hands) underwent surgical correction of clinodactyly using a closing wedge osteotomy. The current study reports on the genetics, clinical presentation, radiological features, and midterm outcome of surgery. RESULTS: Genetic analysis was done in 6 families and confirmed the presence of 2 novel missense mutations (p.Met173Val in 3 families and p.Thr203Asn in 3 families) in the GDF5 gene. All cases in the study group demonstrated the classical clinical and radiographic features of BD type C. However, only 1 hand showed all the features of angel-shaped bony defect. The clinodactyly defect was mostly observed in the index or middle fingers. Surgery for the clinodactyly defect was only done if there was finger overlap. Closing wedge osteotomy was done in a total of 23 digits with a satisfactory outcome. CONCLUSIONS: This study represents the largest reported series of children undergoing surgery for correction of BD type C clinodactyly with a uniform technique performed by a single surgeon. The closing wedge osteotomy used resulted in good midterm outcomes, although long-term follow-up is lacking.


Assuntos
Braquidactilia , Braquidactilia/diagnóstico por imagem , Braquidactilia/genética , Braquidactilia/cirurgia , Criança , Humanos , Osteotomia/métodos , Estudos Retrospectivos , Arábia Saudita , Resultado do Tratamento
19.
Mol Genet Genomic Med ; 10(6): e1951, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35434947

RESUMO

BACKGROUND: Mosaic variegated aneuploidy (MVA) syndrome is a rare, autosomal recessive genetic disease. Here, we report an ultra-rare case of MVA syndrome associated with a CEP57 variant. METHODS: We retrospectively analyzed the clinical data of a 9-year-old female patient and surveyed her family members. Whole-exome sequencing and karyotype analysis were performed; suspected mutations were verified using Sanger sequencing. RESULTS: The patient presented with intrauterine growth restriction, short stature, microcephaly, facial dysmorphism, brachydactyly, and small teeth, and she showed unsatisfactory response to GH replacement therapy. Laboratory tests revealed high insulin-like growth factor-1 levels. Karyotype analysis of the peripheral blood showed mosaic variegated aneuploidies. Whole-exome and Sanger sequencing revealed a novel homozygous nonsense variant, NM_014679.4: c.312 T > G, in CEP57 that leads to translation termination (p.Tyr104*). The parents were heterozygous carriers of the identified variant. CONCLUSION: This study presents an ultra-rare case of CEP57-driven MVA syndrome, identifying a novel homozygous nonsense variant of CEP57 (p.Tyr104*). Our findings enrich the CEP57 mutational spectrum and emphasize the importance of genetic testing in patients with microcephaly and short stature. Furthermore, we conclude that growth hormone treatment is ineffective in such patients.


Assuntos
Braquidactilia , Nanismo , Microcefalia , Aneuploidia , Criança , China , Transtornos Cromossômicos , Nanismo/genética , Feminino , Humanos , Microcefalia/genética , Proteínas Associadas aos Microtúbulos/genética , Mosaicismo , Proteínas Nucleares/genética , Estudos Retrospectivos
20.
Acta Med Indones ; 54(1): 114-119, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35398832

RESUMO

Ciliopathy syndrome is a congenital abnormality of structure and/or function of cilia, which causes pleiotropic disorder, including liver cirrhosis. This study aimed to describe a unique case of liver cirrhosis with possible aetiology of ciliopathy syndrome. A 44 year-old woman with chief complain of hematemesis had diabetes mellitus, obesity, dyslipidaemia, amenorrhoea and often became unconscious. We found short stature, brachydactyly, hyperpigmented maculae in trunk and four limbs, and hepatosplenomegaly. The laboratory results showed: haemoglobin 7.4 g/dl; albumin 2.42 g/dl; urea 84.8 mg/dl; creatinine 2.4 mg/dl; prolactin 138.8 ng/ml, while HBsAg was negative and anti-HCV was non-reactive. Abdominal ultrasonography showed liver cirrhosis; endoscopy showed grade 3 oesophageal varicose; FibroScan showed 75 kPa; liver biopsy showed hydropic degeneration and cirrhosis; and head CT scan showed chronic lacunar infarction of corona radiata and mega cisterna magna occipital. We reported female with oesophageal varicose rupture, short stature, brachydactyly, obesity, diabetes mellitus, dyslipidaemia, hyperpigmented maculae, liver cirrhosis and mega cisterna magna, which was likely to suffer from ciliopathy syndrome.


Assuntos
Braquidactilia , Ciliopatias , Varizes Esofágicas e Gástricas , Adulto , Braquidactilia/patologia , Ciliopatias/patologia , Feminino , Humanos , Fígado/patologia , Cirrose Hepática/complicações , Obesidade
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