Zhang Xiu Quan, Wang Jian, Xiong Fu, Lv Wei Biao, Zhou Yuan Qing, Yang Shao Min, Zhang Yu Ting, Tian Xiao Yan, Lian Wei, Xu Xiang Min
Department of General Laboratories, Reproductive Genetic Research Laboratory, Shunde Hospital, Southern Medical University, Foshan 528300, China.
Department of Obstetrics and Gynecology, Shunde Hospital, Southern Medical University, Foshan 528300, China.
Yi Chuan. 2019 Aug 20;41(8):716-724. doi: 10.16288/j.yczz.19-125.
In order to investigate the genetic variations and the clinical manifestations of a range of congenital ectrodactyly family and to summarize the split hand/foot malformation (SHFM) types and their related pathogenic genes, we conducted phenotypic analyses of patient's limbs by physical and X-ray examination. The haplotypes were analyzed by using the extracted genes from peripheral blood on D10S1709, D10S192, D10S597, D10S1693 and D10S587 loci, and the mutation duplication loci were confirmed by Array-CGH detection. The pathogenic factors and inheritance pattern of SHFM were analyzed based on family investigation and gene analysis. Results demonstrate the proband's phenotype is typically of a congenital SHFM which is manifested by missing bilateral index and middle fingers, short bilateral thumbs, deformed left ring finger with webbing of the skin missing at the middle finger; bilateral big toe with the second and the third toe missing, fourth and fifth toe fusion leading to a deformed toe separated from the first toe by the middle of the foot. The haplotype analyses show that there is a repeat of at least 610 kb in chromosome 10q24.31-10q24.32 region. Array-CGH analysis shows 10q24.31 (102 832 650-103 511 083) ×3. Our results demonstrate that the pathogenic gene variation of ectrodactyly in this family is due to duplication of 10q24.31 (102 832 650103 511 083). The haplotype 165-251-289-219-102 can be used as a disease marker for detecting 10q24.3110q24.32 allele for SHFM.
为了研究一系列先天性缺指（趾）畸形家系的基因变异情况及临床表现，总结裂手/裂足畸形（SHFM）的类型及其相关致病基因，我们通过体格检查和X线检查对患者的肢体进行了表型分析。利用从外周血中提取的基因，对D10S1709、D10S192、D10S597、D10S1693和D10S587位点进行单倍型分析，并通过比较基因组杂交（Array-CGH）检测确认突变重复位点。基于家系调查和基因分析，对SHFM的致病因素和遗传模式进行了分析。结果显示，先证者的表型典型为先天性SHFM，表现为双侧示指和中指缺如、双侧拇指短小、左手环指畸形且中指皮肤蹼状缺如；双侧拇趾缺如，第二和第三趾缺如，第四和第五趾融合导致趾畸形，在足中部与第一趾分离。单倍型分析显示，10号染色体10q24.31-10q24.32区域存在至少610 kb的重复。Array-CGH分析显示10q24.31（102 832 650-103 511 083）×3。我们的结果表明，该家系中缺指（趾）畸形的致病基因变异是由于10q24.31（102 832 650103 511 083）重复所致。单倍型165-251-289-219-102可作为检测SHFM的l0q24.3110q24.32等位基因的疾病标志物。
