PPP2R5D基因变异所致常染色体显性遗传性智力障碍35型1例并文献复习

Mental retardation autosomal dominant 35 caused by de novo missense variants in PPP2R5D gene:a case report and literature review

目的通过分析常染色体显性遗传性智力障碍35型患儿的临床及遗传学特点以提高对该病的认识。方法报道北京儿童医院2018年7月收治的1例常染色体显性遗传性智力障碍35型患者的临床资料、遗传学特点, 并进行文献复习。结果先证者男性, 1岁3个月龄, 表现为发育落后, 低热, 患儿面容特殊(额部突出、鼻梁塌平), 张口呼吸, 肌张力减低。头颅磁共振成像示侧脑室增宽、透明隔间腔及Vergae腔形成、中间帆腔囊肿。基因检测结果示PPP2R5D基因位点新生突变(NM_006245:c.1258G>A, p.E420K)。检索到既往共10篇国外文献报道31例常染色体显性遗传性智力障碍35型患者, 包括本例共32例。32例中临床表现为智力发育迟缓(32例;100.0%)、运动发育迟缓(26例;81.3%)、巨头畸形(26例;81.3%)、癫痫(8例;25.0%), 此外有特殊面容、震颤、眼科异常、骨骼发育异常、心脏畸形等表现。PPP2R5D基因突变均为新生错义突变, 常染色体显性遗传。结论常染色体显性遗传性智力障碍35型主要临床表现为发育迟缓/智力障碍、严重的语言发育落后、巨头畸形、肌张力减低、特殊面容。PPP2R5D基因新生错义突变为本病的遗传学病因。

Objective To enhance understanding of mental retardation autosomal dominant 35(MRD35)by analyzing the clinical and genetic characteristics of the disease.Methods Clinical and genetic data of 1 case of MRD35 in Beijing Children′s Hospital in July 2018 were reported,and literature review was conducted.Results The male proband,1 year and 3 months old,was admitted with the clinical manifestations including mental retardation,low-grade fever,a large forehead,flat nose,open mouth,and hypomyotonia.The brain magnetic resonance imaging showed enlarged lateral ventricles,cavum septum,cavum verge and cavum velum interpositum cyst.The whole exome sequencing test showed that the proband carried a missense mutation c.1258 G>A,(p.E420K)in the PPP2R5D gene,and the mutation was de novo confirmed by Sanger sequencing.There were ten literatures reported,including a total number of 31 cases.Counting on this case,totally 32 cases were included.Among the 32 patients,32 cases(100.0%)had mental retardation,26 cases(81.3%)with motor retardation,26 cases(81.3%)with macrocephaly,8 cases(25.0%)with epilepsy.Facial dysmorphic features,ocular abnormalities,skeletal abnormalities,and cardiac malformations were also reported.All reported individuals had missense mutations of PPP2R5D gene and were autosomal dominantly inherited.Conclusions The main clinical manifestations of MRD35 include growth retardation/mental retardation,severe speech impairment,macrocephaly,hypomyotonia,seizures and dysmorphic facial features.A novel missense mutation in the PPP2R5D gene is the cause of MRD35.