Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan.
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Congenit Anom (Kyoto). 2020 Jul;60(4):115-119. doi: 10.1111/cga.12361. Epub 2019 Oct 29.
Polydactyly is one of the most common congenital abnormal phenotype of autopod, which is characterized by extra supernumerary digit in hands/feet with or without well-developed bony structure within the digits. Preaxial polydactyly (PPD), postaxial polydactyly (PAP), and meso-axial (central) polydactyly are three different isoforms of polydactyly. Genetically, at least 10 genes have been identified causing nonsyndromic polydactyly. In the present study, we have investigated a large family segregating autosomal dominant form of nonsyndromic polydactyly. Whole exome sequencing followed by Sanger sequencing revealed a novel heterozygous missense variant (NM_005269.3; c.1064C>A; p.(Thr355Asn) in the gene GLI1 segregating with the disease phenotype within the family. This study presents first familial case of autosomal dominant form of polydactyly caused by the GLI1 variant.
多指畸形是指手足部出现多余的手指/脚趾,且这些多余的手指/脚趾具有或不具有完整的骨结构,是最常见的一种自发性附肢畸形。根据多余的手指/脚趾位于近侧(桡侧)还是远侧(尺侧),可将其分为轴前型多指(PPD)、轴后型多指(PAP)和中央多指(正中多指)。多指畸形至少由 10 个基因引起,这些基因与常染色体显性遗传的多指畸形有关。本研究调查了一个常染色体显性遗传的非综合征性多指畸形家系,通过全外显子测序和 Sanger 测序发现了一个新的杂合错义突变(NM_005269.3; c.1064C>A; p.(Thr355Asn)),该突变位于 GLI1 基因中,与家系中的疾病表型共分离。本研究报道了首例由 GLI1 突变引起的常染色体显性遗传的多指畸形家系。