Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Institute of Human Genetics, University of Ulm, Ulm, Germany.
Hum Genet. 2019 Jun;138(6):593-600. doi: 10.1007/s00439-019-02000-0. Epub 2019 Apr 13.
Postaxial polydactyly (PAP) is a common limb malformation that often leads to cosmetic and functional complications. Molecular evaluation of polydactyly can serve as a tool to elucidate genetic and signaling pathways that regulate limb development, specifically, the anterior-posterior specification of the limb. To date, only five genes have been identified for nonsyndromic PAP: FAM92A, GLI1, GLI3, IQCE and ZNF141. In this study, two Pakistani multiplex consanguineous families with autosomal recessive nonsyndromic PAP were clinically and molecularly evaluated. From both pedigrees, a DNA sample from an affected member underwent exome sequencing. In each family, we identified a segregating frameshift (c.591dupA [p.(Q198Tfs21)]) and nonsense variant (c.2173A > T [p.(K725)]) in KIAA0825 (also known as C5orf36). Although KIAA0825 encodes a protein of unknown function, it has been demonstrated that its murine ortholog is expressed during limb development. Our data contribute to the establishment of a catalog of genes important in limb patterning, which can aid in diagnosis and obtaining a better understanding of the biology of polydactyly.
轴后多指（PAP）是一种常见的肢体畸形，常导致美容和功能并发症。多指的分子评估可作为阐明调节肢体发育的遗传和信号通路的工具，特别是肢体的前后规范。迄今为止，已鉴定出五个非综合征性 PAP 的基因：FAM92A、GLI1、GLI3、IQCE 和 ZNF141。在这项研究中，对来自两个巴基斯坦的常染色体隐性非综合征性 PAP 的多灶近亲家族进行了临床和分子评估。从两个家系中，受影响成员的 DNA 样本进行了外显子组测序。在每个家庭中，我们都鉴定出 KIAA0825（也称为 C5orf36）中存在一个可分离的移码突变（c.591dupA [p.(Q198Tfs21)]) 和无义突变（c.2173A > T [p.(K725)])。尽管 KIAA0825 编码一个未知功能的蛋白质，但已经证明其鼠类同源物在肢体发育过程中表达。我们的数据有助于建立一个在肢体模式形成中起重要作用的基因目录，这有助于诊断和更好地理解多指畸形的生物学。
