Shi Lijing, Huang Hui, Jiang Qiuxia, Huang Rongsen, Fu Wanyu, Mao Liangwei, Wei Xiaoming, Cui Huanhuan, Lin Keke, Cai Licheng, Yang You, Wang Yuanbai, Wu Jing
Department of Ultrasound, Quanzhou Women's and Children's Hospital, Quanzhou, China.
BGI Genomics, BGI-Shenzhen, Shenzhen, China.
Front Genet. 2020 Feb 28;11:130. doi: 10.3389/fgene.2020.00130. eCollection 2020.
Syndactyly is one of the most frequent hereditary limb malformations with clinical and genetical complexity. Autosomal dominant syndactyly type IV (SD4) is a rare form of syndactyly, caused by heterozygous mutations in a sonic hedgehog () regulatory element () which resides in intron 5 of the gene on chromosome 7q36.3. SD4 is characterized by complete cutaneous syndactyly of the fingers, accompanied by cup-shaped hands due to flexion of the fingers and polydactyly. Here, for the first time, we reported a large Chinese family from Fujian province, manifesting cup-shaped hands consistent with SD4 and intrafamilial heterogeneity in clinical phenotype of tibial and fibulal shortening, triphalangeal thumb-polysyndactyly syndrome (TPTPS). We identified a novel duplication of ∼222 kb covering exons 2-17 of the gene in this family by sub-exome target sequencing. This case expands our new clinical understanding of SD4 phenotype and again confirms the feasibility to detect copy number variation by sub-exome target sequencing.
并指畸形是最常见的遗传性肢体畸形之一，具有临床和遗传复杂性。常染色体显性IV型并指畸形（SD4）是并指畸形的一种罕见形式，由位于7号染色体q36.3上的音猬因子（SHH）调控元件（ZRS）中的杂合突变引起。SD4的特征是手指完全皮肤并指，伴有因手指屈曲和多指畸形导致的杯状手。在此，我们首次报道了一个来自福建省的大型中国家系，表现出与SD4一致的杯状手，以及胫腓骨缩短、三节拇指-多指畸形综合征（TPTPS）临床表型的家族内异质性。我们通过外显子组靶向测序在这个家系中鉴定出一个约222 kb的新重复，覆盖SHH基因的外显子2-17。该病例扩展了我们对SD4表型的新临床认识，并再次证实了通过外显子组靶向测序检测拷贝数变异的可行性。
