一个与 Grebe 型软骨发育不良和短指畸形 C+共分离的 GDF5 移码突变：临床报告和迷你综述。

A GDF5 frameshift mutation segregating with Grebe type chondrodysplasia and brachydactyly type C+ in a 6 generations family: Clinical report and mini review.

机构信息

Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE) College, PIEAS, Faisalabad, Pakistan; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.

Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.

出版信息

Eur J Med Genet. 2021 Jul;64(7):104226. doi: 10.1016/j.ejmg.2021.104226. Epub 2021 Apr 16.

DOI:10.1016/j.ejmg.2021.104226

PMID:33872773

Abstract

Different mutations in the Growth/Differentiation Factor 5 gene (GDF5) have been associated with varying types of skeletal dysplasia, including Grebe type chondrodysplasia (GTC), Hunter-Thompson syndrome, Du Pan Syndrome and Brachydactyly type C (BDC). Heterozygous pathogenic mutations exert milder effects, whereas homozygous mutations are known to manifest more severe phenotypes. In this study, we report a GDF5 frameshift mutation (c.404delC) segregating over six generations in an extended consanguineous Pakistani family. The family confirmed that both GTC and BDC are part of the GDF5 mutational spectrum, with severe GTC associated with homozygosity, and with a wide phenotypic variability among heterozygous carriers, ranging from unaffected non-penetrant carriers, to classical BDC and to novel unclassified types of brachydactylies.

摘要

生长/分化因子 5 基因（GDF5）的不同突变与各种类型的骨骼发育不良有关，包括 Grebe 型软骨发育不良（GTC）、Hunter-Thompson 综合征、Du Pan 综合征和短指型 C 型（BDC）。杂合致病性突变的作用较轻，而纯合突变已知表现出更严重的表型。在这项研究中，我们报告了一个 GDF5 移码突变（c.404delC）在一个扩展的近亲巴基斯坦家族中跨越六代遗传。该家族证实 GTC 和 BDC 均属于 GDF5 突变谱的一部分，严重的 GTC 与纯合性有关，而杂合子携带者的表型变异广泛，从无影响的非穿透携带者，到经典的 BDC，再到新型未分类的短指类型。