一例罕见的3-磷酸甘油酸脱氢酶缺乏症患儿的临床表现及遗传学分析

Genetic and phenotypic analysis of a patient with phosphogylcerate dehydrogenase deficiency

目的探讨1例以眼底异常为主要表现,伴小头畸形、生长发育迟缓和宫内生长受限的女性患儿的遗传学病因。方法对患儿进行眼科检查,包括眼前段照相、眼底彩照、荧光素眼底血管造影,并对患儿及父母进行全外显子组测序,对候选变异进行Sanger测序验证。结果患儿双眼虹膜残膜,下方虹膜缺损,黄斑发育不良,颞上、下血管弓附近有放射状或线形排列的纺锤形脱色素。测序结果显示患儿携带PHGDH基因c.196G>A和c.1177G>A错义变异,分别遗传自其父母,蛋白预测结果为有害。结论患儿被诊断为罕见PHGDH基因变异导致的磷酸甘油酸脱氢酶缺乏症。本研究结果扩展了该病相关的眼科表现。

Objective To explore the genetic basis for a child with ocular anomaly,microcephaly,growth retardation and intrauterine growth restriction.Methods The patient underwent ophthalmologic examination,including anterior segment photography,fundus color photography,and fundus fluorescein angiography.The patient and her parents were subjected to whole exome sequencing.Candidate variants were verified by Sanger sequencing and bioinformatic analysis.Results The patient was found to have bilateral persistent pupillary membrane and coloboma of inferior iris,in addition with macular dysplasia and radial pigmentation near the hemal arch of the temporal retina.She was found to have carried compound heterozygous missense variants of the PHGDH gene,namely c.196G>A and c.1177G>A,which were respectively inherited from her parents.Bioinformatic analysis suggested both variants to be pathogenic.Conclusion The patient was diagnosed with phosphoglycerate dehydrogenase deficiency.Above finding has enriched the phenotypic spectrum of the disease with ocular manifestations.