一个X连锁显性遗传Nance-Horan综合征家系致病突变的遗传学研究

目的对中国东北辽宁地区一个三代后极性先天性白内障合并小眼球小角膜家系进行致病变异筛查，为临床明确诊断及遗传咨询提供必要的遗传学依据。 方法2017年4月采集该家系中2例患者和1例正常对照者的外周静脉血，提取基因组脱氧核糖核酸，对先证者进行眼部检查。通过MiSeq测序平台对4813个临床疾病相关基因进行高通量测序，寻找致病变异位点。 结果该家系表现为后极性先天性白内障伴有小眼球小角膜，呈X连锁显性遗传。对家系中3个成员基因组脱氧核糖核酸进行测序，发现家系内患者携带X染色体NHS基因无义突变(NHS c．742C>T，p.R248^*)，该突变在家系中与疾病表型共分离。通过查询人类基因突变数据库，该突变为Nance-Horan综合征致病突变，患者临床表现与该综合征相符。 结论该家系诊断为Nance-Horan综合征，NHS基因c.742C>T(p.R248^*)突变是该家系的致病变异。

Pathogenic mutation in a family with X-linked dominant Nance-Horan syndrome

ObjectiveThe aim of this study was to screen the pathogenic mutation of three generation post polar congenital cataract with small eyeball and small cornea, and provide necessary genetic evidence for clinical diagnosis and genetic counseling. MethodsIn April 2017, Peripheral venous blood from 2 patients and a normal control case was collected; genomic deoxyribonucleic acid was extracted, and the ocular examination was done for proband. The 4813 clinical disease related genes were sequenced by high throughput sequencing based on MiSeq sequencing platform for seeking the pathogenic mutation. ResultsThe family was characterized by posterior polar congenital cataract with small eyeball and small cornea, which was X dominant inheritance. The genomic deoxyribonucleic acid of 3 members of the family was sequenced, and the patients were found to carry the NHS gene non sense mutation (NHS c. 742C>T, p. R248^*) on the chromosome X, which was co-separated with the disease phenotype in the family. After comparing with Human Gene Mutation Database, the mutation is pathogenic for Nance-Horan syndrome which were consistent with the clinical manifestations of the patients. ConclusionsThe family is diagnosed as Nance-Horan syndrome, and the mutation of NHS gene c. 742C>T (p.R248^*) is the pathogenic variation of this family.