PIK3R2基因错义变异所致MPPH综合征I型患儿遗传学分析

目的：总结1例罕见的巨脑畸形-多小脑回-多指（趾）畸形-脑积水（MPPH）综合征Ⅰ型患儿的临床特点及基因检测结果。方法：回顾性总结2021 年1月在温州医科大学附属第一医院新生儿科确诊的1例MPPH I型患儿的临床表现、影像学检查和基因检测结果等病例资料。并通过文献复习，分析和总结国内外已报道的MPPH I型综合征病例的临床特征及遗传学特点。同时对患儿进行全外显子组检测，对候选变异用Sanger测序进行家系验证。结果：先证者携带PIK3R2 基因c.1117（p.Gly373Arg）杂合错义变异，国内既往未见报道，其父母未携带相同变异。相关文献报道的16例MPPH I型患儿主要表现为不同程度的脑积水、巨脑畸形、癫痫发作、多指（趾）畸形、发育迟缓及智力发育障碍。共报道了3个基因突变位点，其中p.Gly373Arg杂合变异最多（14例），罕见变异包括p.Leu401Pro变异1例和p.Asp557His变异1例。结论：PIK3R2 基因c.1117G＞A（p.Gly373Arg）杂合错义变异可能是该患儿发生MPPH I的原因，脑积水考虑与该综合征相关，其母亲再次怀孕时需接受产前诊断。

Children with MPPH I syndrome due to missense variant of PIK3R2 gene: A case analysis

Objective: To summarize the clinical features and make a genetic analysis of a patient with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome I (MPPH I). Methods: We retrospectively collected the clinical manifestations, imaging examinations and genetic analysis of a neonate with MPPH type I which was diagnosed at the Department of Neonatology of the First Affiliated Hospital of Wenzhou Medical University in January 2021. Literature was retrieved to summarize the clinical and genetic characteristic of MPPH type I casued by PIK3R2 variant. Whole exome sequencing was carried out for the proband. Candidate variant was verified by Sanger sequencing. Results: The proband was found to harbor a heterozygous missense c.1117G>A (p.Gly373Arg) variant of the PIK3R2 gene, which was unreported previously in China. The variant was not detected in either parent. The clinical characteristics of the 16 cases reported in the relevant literature review mainly presented a constellation of neurodevelopmental disorder, including megalencephaly, polymicrogyria,and hydrocephalus, and multiple neurological symptoms, including intellectual disability and epilepsy. PIK3R2 gene variants were identified, and most of them were p.Gly373Arg variant in exon 10 (fourteen cases), followed by p.Leu401Pro (one case), p.Asp557His (one case). Conclusion: The PIK3R2 gene c.1117G>A (p.Gly373Arg) variant may underlay the MPPH I syndrome in this patient. Hydrocephalus may be related to MPPH syndrome.Prenatal diagnosis is recommended for subsequent pregnancies.