一个眼-脑-肾综合征家系的OCRL基因变异研究  

Analysis of OCRL gene variant in a Chinese pedigree affected with Lowe syndrome

作　　者：周新龙[1] 王清明 邹姒妮[1] 洪晓纯[1] 袁海明 Zhou Xinlong;Wang Qingming;Zou Sini;Hong Xiaochun;Yuan Haiming(Dongguan Maternal and Child Health Care Hospital,Dongguan,Guangdong 523120,China;Dongguan Institute of Reproductive and Genetic Research,Dongguan,Guangdong 523120,China)

机构地区：[1]东莞市妇幼保健院,广东523120 [2]东莞市生殖遗传研究所,广东523120

出　　处：《中华医学遗传学杂志》2022年第1期56-59,共4页Chinese Journal of Medical Genetics

基　　金：东莞市社会科技发展重点项目(202050715007220)。

摘　　要：目的探讨一个眼-脑-肾综合征(Lowe综合征)家系基因型与表型的关系,为遗传咨询提供依据。方法应用全外显子测序(whole exome sequencing,WES)结合Sanger技术对先证者及其家系成员进行基因变异分析,对患者临床表型与以往文献比较。结果先证者为一名3岁5个月男性患儿,临床表现为先天性白内障、青光眼,脑发育不良、认知损害,肾功能异常等多发性先天异常。WES检测到OCRL基因发生半合子错义变异NM_000276.3:c.1255T>C(p.Trp419Arg)(GRCh37/hg19),该变异在以往的文献和数据库中未见报道,为新变异。Sanger测序证实该变异遗传自表型正常的母亲,通过对外祖父、外祖母进一步分析证实为新发变异,患儿哥哥体健且未携带该变异,故根据美国医学遗传学与基因组学会/分子病理学协会指南判定为临床致病性,为患儿致病原因。通过与以往报道的Lowe综合征病例进行比较发现,先证者除了表现出Lowe综合征典型临床特征外,还表现出该综合征罕有的表型如先天性喉骨软化、皮脂腺囊肿、反复湿疹、隐睾、低血糖、易怒等。患儿颅脑磁共振成像显示胼胝体发育不良,脑白质偏少,脑发育不全,这在以往文献中未见报道。结论本研究结果扩展了OCRL基因突变谱,丰富了Lowe综合征临床表型,并为家系的遗传咨询提供了依据。Objective To explore the genotype-phenotype correlation of a Chinese pedigree affected with Lowe syndrome.Methods Whole exome sequencing(WES)and Sanger sequencing were carried out for the proband and members of his pedigree.Results The proband,a 3-year-and-5-month-old male,presented with multiple anomalies including congenital cataract,glaucoma,brain dysplasia,renal dysfunction and cognitive impairment.WES revealed that he has harbored a novel hemizygous missense variant of the OCRL gene,namely NM_000276.3:c.1255T>C(p.Trp419Arg)(GRCh37/hg19),which was derived from his unaffected mother.The same variant was not found in his elder brother who was healthy.The variant was predicted to be pathogenic according to ACMG/AMP guideline.Compared with previously reported cases of Lowe syndrome,our patient has displayed rare features including corpus callosum dysplasia,reduction of white matter,cerebral hypoplasia,laryngomalacia,sebaceous cyst,recurrent eczema,cryptorchidism,hypoglycemia and irritability.Conclusion Above finding has expanded the mutational spectrum of the OCRL gene,enriched clinical features of Lowe syndrome,and enabled genetic counseling for this pedigree.

关 键 词：OCRL基因 Lowe综合征 先天性白内障 脑发育不良 肾功能异常 全外显子测序 

分 类 号：R725.9[医药卫生—儿科]