NFIA基因突变致脑畸形伴或不伴尿道缺陷疾病诊治分析

Brain malformation with or without urethral defect due to NFIA gene mutation:one case report with a literature review

目的探讨1例NFIA基因突变致脑畸形伴或不伴尿道缺陷疾病(brain malformations with or without urinary tract defects,BRMUTD,PMID:25714559)患者的临床特点和基因突变特征。方法收集湖南省儿童医院神经外科收治的1例NFIA基因突变致BRMUTD患者的临床资料,应用二代测序和Sanger测序技术对其进行基因突变分析,并通过文献检索,对有关NFIA基因突变及染色体1p32-p31缺失、临床表现为脑畸形伴或不伴尿道缺陷疾病相关文献共27例病例进行复习。结果患者为女性,表现有胼胝体偏小、脑室扩大、智力发育落后、颅缝早闭、小脑扁桃体下疝(又称Chiari畸形)、肝功能异常等多系统问题;基因检测结果显示患者携带NFIA基因c.1051C>T(p.Arg351*)的杂合突变,该突变是新发突变,且在gnomAD数据库与ExAC数据库中未见报道;生物学信息分析软件分析预测提示为致病突变。通过检索文献数据库,联合本中心1例患者,共纳入27例脑畸形伴或不伴尿道缺陷疾病患者的临床特点与基因突变特征,其中男女比例为15∶12,其中胼胝体异常(24/27)、脑室扩大(23/27)、巨头畸形(22/27)、狭颅症(5/27)、发育迟滞(25/27)、Chiari畸形(7/27)、泌尿系统疾病(10/27)较为常见。结论NFIA基因突变新的致病位点c.1051C>T(p.Arg351*),丰富了NFIA的突变谱,通过分析脑畸形伴或不伴尿道缺陷疾病患者临床表现分析,加深了对脑畸形伴或不伴尿道缺陷疾病的认识。

Objective To explore the clinical characteristics and gene mutation status of a child with brain malformation with or without urethral defects due to NFIA gene mutation and improve the understanding of the disease.Methods Clinical data were collected from a child with brain malformations with or without urethral defects due to NFIA gene mutation.Next-generation and Sanger sequencing technologies were utilized for examining the mutations.And a literature search was performed for reviewing the medical records of 27 cases related to NFIA gene mutations and chromosome 1p32-p31 deletions.Results The child was a female with multiple system problems of small corpus callosum,enlarged ventricles,retarded mental development,craniosynostosis,Arnold-Chiari malformation and abnormal liver function.Genetic testing indicated that she carried the NFIA gene c.1051C>T(p.Arg351*)heterozygous mutation,a new mutation and not previously reported in the databases of gnomAD and ExAC;analysis and prediction of biological information analysis software hinted at a pathogenic mutation.Through searching the literature database,one child of our center was added for analyzing clinical characteristics and gene mutation characteristics of a total of 27 children with brain malformations with or without urethral defects.The ratio of male-to-female was 15:12.There were corpus callosum abnormality(24/27),enlarged ventricles(23/27),macrocephaly(22/27),craniosynostosis(5/27),developmental delay(25/27),Arnold-Chiari malformation(7/27)and urinary system disease(10/27).Conclusion The new pathogenic site c.1051C>T(p.Arg351*)of NFIA gene mutations enriches the mutation spectrum of NFIA.By analyzing the clinical manifestations of children with brain malformations with or without urethral defects,we deepens the understanding of brain malformations with or without urethral defects.