Tian Qi, Li Yunping, Kousar Rizwana, Guo Hui, Peng Fenglan, Zheng Yu, Yang Xiaohua, Long Zhigao, Tian Runyi, Xia Kun, Lin Haiying, Pan Qian
State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan, China.
Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
BMC Med Genet. 2017 Jan 7;18(1):2. doi: 10.1186/s12881-016-0360-9.
Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males.
Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome. Whole-exome sequencing combined with RT-PCR and Sanger sequencing was used to search for a genetic cause underlying the disease phenotype.
Whole-exome sequencing identified in all affected individuals of the family a novel donor splicing site mutation (NM_198270: c.1045 + 2T > A) in intron 4 of the gene NHS, which maps to chromosome Xp22.13. The identified mutation results in an RNA processing defect causing a 416-nucleotide addition to exon 4 of the mRNA transcript, likely producing a truncated NHS protein.
The donor splicing site mutation NM_198270: c.1045 + 2T > A of the NHS gene is the causative mutation in this Nance-Horan Syndrome family. This research broadens the spectrum of NHS gene mutations, contributing to our understanding of the molecular genetics of NHS.
南斯-霍兰综合征（NHS）（OMIM：302350）是一种罕见的X连锁发育障碍，其特征为双侧先天性白内障，偶尔伴有牙齿异常、特征性的畸形面容、掌骨短小和智力发育迟缓。携带该致病基因的女性表现出的症状较男性患者轻。
在此，我们报告了一个四代的中国家庭，其中有多名个体患有南斯-霍兰综合征。采用全外显子组测序结合逆转录聚合酶链反应（RT-PCR）和桑格测序法来寻找导致该疾病表型的遗传原因。
全外显子组测序在该家庭所有患病个体中发现了NHS基因第4内含子的一个新的供体剪接位点突变（NM_198270：c.1045+2T>A），该基因位于X染色体p22.13。所鉴定出的突变导致RNA加工缺陷，使mRNA转录本的外显子4额外增加了416个核苷酸，可能产生截短的NHS蛋白。
NHS基因的供体剪接位点突变NM_198270：c.1045+2T>A是这个南斯-霍兰综合征家庭的致病突变。本研究拓宽了NHS基因突变谱，有助于我们对NHS分子遗传学的理解。
