Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Department of Radiology, the Third Xiangya Hospital, Central South University, Changsha, China.
Curr Mol Med. 2019;19(3):228-235. doi: 10.2174/1566524019666190308110122.
Polydactyly, characterized by supernumerary digits in the upper or lower extremities, is the most common congenital digital abnormalities. It derives from the defective patterning of anteroposterior axis of the developing limb, with various etiology and clinical heterogeneity. The patients with post-axial polydactyly type A (PAPA) have the typical symptom of a well-formed supernumerary digit outside the fifth digit.
The aim of present study was to identify the causative mutations of two unrelated Han Chinese patients with non-syndromic PAPA.
Two unrelated Han Chinese patients and 100 ethnicity-matched, unrelated normal controls were recruited for this study. BGISEQ-500 exome sequencing was performed in the two patients, followed by validation in the patients and 100 controls by using Sanger sequencing.
Two mutations in the GLI family zinc finger 3 gene (GLI3), including a frameshift mutation c.3437_3453delTCGAGCAGCCCTGCCCC (p.L1146RfsX95) and a nonsense mutation c.3997C>T (p.Q1333X), were identified in two patients but were absent in the 100 healthy controls.
The two GLI3 mutations, p.L1146RfsX95 and p.Q1333X, may account for non-syndromic PAPA in the two patients, respectively. The findings of this study may expand the mutational spectrum of GLI3-PAPA and provide novel insights into the genetic basis of polydactyly.
多指畸形是一种常见的先天性指（趾）畸形，表现为上肢或下肢出现多余的手指（趾）。其发生是由于肢体前后轴发育异常，具有多种病因和临床异质性。轴后型多指畸形 A 型（PAPA）患者的典型症状是在第五指外侧有一个形态良好的多余指。
本研究旨在鉴定 2 例非综合征性 PAPA 汉族患者的致病突变。
纳入 2 例汉族非综合征性 PAPA 患者和 100 例汉族无关正常对照进行研究。对 2 例患者进行 BGISEQ-500 外显子组测序，然后对患者和 100 例对照进行 Sanger 测序验证。
在 2 例患者中发现 GLI 家族锌指蛋白 3 基因（GLI3）中的 2 个突变，包括移码突变 c.3437_3453delTCGAGCAGCCCTGCCCC（p.L1146RfsX95）和无义突变 c.3997C>T（p.Q1333X），但在 100 例健康对照中均未发现。
p.L1146RfsX95 和 p.Q1333X 这 2 个 GLI3 突变可能分别导致了这 2 例患者的非综合征性 PAPA。本研究的发现可能扩展了 GLI3-PAPA 的突变谱，为多指畸形的遗传基础提供了新的见解。
