肿瘤蛋白p63是调控上皮形态发生的重要转录因子。已知与TP63基因相关的变体会导致多种疾病。在这项研究中,我们确定了中国家系中手/足分裂畸形的遗传原因。
对于这项研究,我们招募了一个中国家庭,并从该家庭的受影响个体和正常个体(三个受影响个体和两个正常个体)收集了样本。进行全外显子组测序以检测该家族中潜在的遗传缺陷。使用Sanger测序方法验证潜在变体。
使用全外显子组和Sanger测序,我们在TP63(NM_003722.5:c.921G>T;p.Met307Ile)中鉴定出一种新的杂合致病性错义变体。该变体导致甲硫氨酸被异亮氨酸取代。结构分析表明p63蛋白的关键功能结构域的结构发生了变化。
这种新颖的错义变异扩展了TP63变异谱,并为患有手/足分裂畸形或其他TP63相关疾病的家庭的遗传咨询和产前诊断提供了基础。
Tumor protein p63 is an important transcription factor regulating epithelial morphogenesis. Variants associated with the TP63 gene are known to cause multiple disorders. In this study, we determined the genetic cause of split-hand/foot malformation in a Chinese pedigree.
For this study, we have recruited a Chinese family and collected samples from affected and normal individuals of the family (three affected and two normal). Whole exome sequencing was performed to detect the underlying genetic defect in this family. The potential variant was validated using the Sanger sequencing approach.
Using whole-exome and Sanger sequencing, we identified a novel heterozygous pathogenic missense variant in TP63 (NM_003722.5: c.921G > T; p.Met307Ile). This variant resulted in the substitution of methionine with isoleucine. Structural analysis suggested a resulting change in the structure of a key functional domain of the p63 protein.
This novel missense variant expands the TP63 variant spectrum and provides a basis for genetic counseling and prenatal diagnosis of families with split-hand/foot malformation or other TP63-related diseases.