一例OCRL基因外显子重复变异所致的眼脑肾综合征患儿的临床及遗传学分析

目的探讨1例表现为先天性白内障、脑发育迟缓、蛋白尿的男性患儿的遗传学病因。方法收集患儿的临床资料,采集患儿及其正常表型的亲代的外周血样,提取基因组DNA,应用高通量测序法筛查OCRL基因的变异,并用定量PCR法进行验证。通过变异序列分析和PubMed检索,预测候选变异的致病性。结果患儿曾接受先天性白内障手术,脑发育迟缓,脑部成像显示脑沟裂增宽、双侧额颞部蛛网膜下腔增宽、脑室后角旁白质髓鞘化不良等,此外有蛋白尿及双肾弥漫性回声。患儿X染色体OCRL基因第5~16外显子存在重复变异。患儿母亲为该变异的携带者,父亲未携带。结论OCRL基因第5~16外显子重复变异是该患儿的发病原因。由OCRL基因外显子重复所致的眼脑肾综合征尚无文献报道。鉴于眼脑肾综合征临床表现的异质性,基因检测对于该病的确诊具有重要的意义。

Clinical and genetic analysis of an infant with Lowe syndrome caused by exonic duplication of OCRL gene

Objective To explore the genetic basis of an infant featuring congenital cataract,developmental delay and proteinuria.Methods Clinical data and peripheral blood samples of the family were collected.Potential variants were screened by using targeted capture and high-throughput sequencing on a NextSeq 500 platform.Suspected variant was verified by quantitative PCR.Pathogenicity of the candidate variant was predicted based on clinical presentation and laboratory tests.Results The infant’s phenotypes included brain development retardation and proteinuria.Cranial MRI indicated widening of cerebral fissure,bilateral frontal and temporal subarachnoid cavities,and dysplasia of white matter myelination in posterior angular of ventricle.A novel duplication of exons 5 to 16 of the OCRL gene was found in the patient.His mother has carried the same duplication variant.Conclusion The duplication variant of the OCRL gene probably underlies the oculo-cerebro-renal syndrome in the infant.Due to the heterogeneity of its clinical manifestation,pertinent genetic detection is essential for acurrate diagnosis of patients who have the related phenotypes.