Muthusamy Babylakshmi, Nguyen Thong T, Bandari Aravind K, Basheer Salah, Selvan Lakshmi Dhevi N, Chandel Deepshikha, Manoj Jesna, Gayen Srimonta, Seshagiri Somasekar, Chandra Girimaji Satish, Pandey Akhilesh
Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India; Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Department of Molecular Biology and Metabolic Disease, Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
Eur J Med Genet. 2020 Jan;63(1):103635. doi: 10.1016/j.ejmg.2019.02.007. Epub 2019 Feb 21.
Say-Meyer syndrome is a rare and clinically heterogeneous syndrome characterized by trigonocephaly, short stature, developmental delay and hypotelorism. Nine patients with this syndrome have been reported thus far although no causative gene has yet been identified. Here, we report two siblings with clinical phenotypes of Say-Meyer syndrome with moderate to severe intellectual disability and autism spectrum disorder. Cytogenetics and array-based comparative genomic hybridization did not reveal any chromosome abnormalities or copy number alterations. Exome sequencing of the patients revealed a novel X-linked recessive splice acceptor site variant c.145-2A > G in intron 5 of HUWE1 gene in both affected siblings. RT-PCR and sequencing revealed the use of an alternate cryptic splice acceptor site downstream, which led to deletion of six nucleotides resulting loss of two amino acids p.(Cys49-Glu50del) in HUWE1 protein. Deletion of these two amino acids, which are located in a highly conserved region, is predicted to be deleterious and quite likely to affect the function of HUWE1 protein. This is the first report of a potential candidate gene mutation for Say-Meyer syndrome, which was initially described four decades ago.
赛-迈耶综合征是一种罕见的临床异质性综合征，其特征为三角头畸形、身材矮小、发育迟缓及眼距过窄。迄今为止，已有9例该综合征患者被报道，但尚未鉴定出致病基因。在此，我们报告了两名患有赛-迈耶综合征临床表型的同胞，伴有中度至重度智力残疾和自闭症谱系障碍。细胞遗传学和基于阵列的比较基因组杂交未发现任何染色体异常或拷贝数改变。对患者进行外显子组测序发现，两名患病同胞的HUWE1基因第5内含子中存在一个新的X连锁隐性剪接受体位点变异c.145-2A＞G。逆转录聚合酶链反应（RT-PCR）和测序显示使用了下游一个隐蔽的替代剪接受体位点，导致6个核苷酸缺失，致使HUWE1蛋白中两个氨基酸（p.(Cys49-Glu50del)）缺失。这两个氨基酸位于一个高度保守区域，其缺失预计具有有害性，很可能会影响HUWE1蛋白的功能。这是关于赛-迈耶综合征潜在候选基因突变的首次报道，该综合征最初于40年前被描述。
