Acromesomelic Dysplasia With Homozygosity for a Likely Pathogenic BMPR1B Variant: Postaxial Polydactyly as a Novel Clinical Finding.

IF 1.5 4区 医学 Q4 GENETICS & HEREDITY
Ibrahim M Abdelrazek, Alexej Knaus, Behnam Javanmardi, Peter M Krawitz, Denise Horn, Ebtesam M Abdalla, Sheetal Kumar
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引用次数: 0

Abstract

Background: Acromesomelic chondrodysplasias are a rare subgroup of the clinically and genetically heterogeneous osteochondrodysplasias that are characterised by abnormalities in the limb development and short stature. Here, we report a 2-year-old boy, offspring of consanguineous parents, with acromesomelic dysplasia and postaxial polydactyly in which exome sequencing identified a novel homozygous missense variant in BMPR1B. The patient showed skeletal malformation of both hands and feet that included complex brachydactyly with the thumbs most severely affected, postaxial polydactyly of both hands, shortened toes as well as a bilateral hypoplasia of the fibula.

Methods: Whole trio exome sequencing was conducted to identify potential genetic variants in the patient.

Results: The analysis identified the biallelic variant NM_001203.3:c.821A > G;p.(Gln274Arg) in BMPR1B, a gene encoding bone morphogenetic protein receptor 1B.

Conclusion: The skeletal phenotype can be brought in line with the phenotypes of previously reported cases of BMPR1B-associated chondrodysplasias. However, the postaxial polydactyly described here is a novel clinical finding in a BMPR1B-related case; notably, it has previously been reported in other acromesomelic dysplasia cases caused by homozygous pathogenic variants in GDF5-a gene which encodes for growth differentiation factor 5, a high-affinity ligand to BMPR1B.

伴有可能致病的 BMPR1B 变异的畸形发育不良:后轴多指畸形是一种新的临床发现
背景:尖头畸形软骨发育不良症是临床和遗传异质性骨软骨发育不良症中的一个罕见亚组,其特点是肢体发育异常和身材矮小。这里,我们报告了一名 2 岁男童,其父母均为近亲结婚,患有尖头骨发育不良和轴后多指畸形,外显子组测序发现了 BMPR1B 中的一个新型同态错义变异。该患者的双手和双脚均出现骨骼畸形,包括拇指受影响最严重的复杂肱骨畸形、双手轴后多指畸形、脚趾缩短以及双侧腓骨发育不良:方法:对患者进行了全三组外显子测序,以确定潜在的遗传变异:结果:分析发现了编码骨形态发生蛋白受体1B的基因BMPR1B中的双倍序列变体NM_001203.3:c.821A > G;p.(Gln274Arg) :结论:该病例的骨骼表型与之前报道的 BMPR1B 相关软骨发育不良病例的表型一致。然而,这里描述的轴后多指畸形在 BMPR1B 相关病例中是一个新的临床发现;值得注意的是,此前曾有报道称,在其他由 GDF5(编码生长分化因子 5 的基因,该基因是 BMPR1B 的高亲和性配体)同基因致病变体引起的尖状骨发育不良病例中也出现过这种情况。
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来源期刊
Molecular Genetics & Genomic Medicine
Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.20
自引率
0.00%
发文量
241
审稿时长
14 weeks
期刊介绍: Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.
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