Sutani Akito, Shima Hirohito, Hijikata Atsushi, Hosokawa Susumu, Katoh-Fukui Yuko, Takasawa Kei, Suzuki Erina, Doi Shozaburo, Shirai Tsuyoshi, Morio Tomohiro, Fukami Maki, Kashimada Kenichi
Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Eur J Med Genet. 2020 Jan;63(1):103626. doi: 10.1016/j.ejmg.2019.01.016. Epub 2019 Jan 31.
10q26 deletion syndrome is caused by a rare chromosomal abnormality, and patients with this syndrome present with an extensive and heterogeneous phenotypic spectrum. Several genes, such as EMX2 and FGFR2, were identified as the cause genital anomalies and facial dysmorphism in 10q26 deletion syndrome. However, the critical region for 10q26 deletion syndrome is not determined and the precise relationships between the causative genes and the phenotypes are still controversial. WD repeat domain 11 (WDR11), located at 10q25-26, was recently identified as a causative gene in hypogonadotropic hypogonadism, but other clinical phenotypes caused by WDR11 variants have not been identified. In this study, we have identified a WDR11 missense mutation, NM_018117.11: c.2108G > A; p.(Arg703Gln); ClinVar accession SCV000852064, in a two-year-old boy with severe growth retardation, ventricular septal defect, and coloboma symptoms. The case suggests that WDR11 is partially responsible for the clinical features of 10q26 deletion syndrome and provides novel insights into the pathophysiology of this syndrome.
10q26缺失综合征由一种罕见的染色体异常引起，该综合征患者表现出广泛且异质性的表型谱。几个基因，如EMX2和FGFR2，被确定为10q26缺失综合征中生殖器异常和面部畸形的病因。然而，10q26缺失综合征的关键区域尚未确定，致病基因与表型之间的确切关系仍存在争议。位于10q25 - 26的WD重复结构域11（WDR11）最近被确定为低促性腺激素性性腺功能减退的致病基因，但尚未发现由WDR11变异引起的其他临床表型。在本研究中，我们在一名患有严重生长发育迟缓、室间隔缺损和缺损症状的两岁男孩中鉴定出一个WDR11错义突变，NM_018117.11: c.2108G > A; p.(Arg703Gln); ClinVar登录号SCV000852064。该病例表明WDR11部分导致了10q26缺失综合征的临床特征，并为该综合征的病理生理学提供了新的见解。
