三种导致先天性肾病综合征婴儿的 NPHS1 基因突变：两个中国（汉族）病例。

Three Novel Heterozygous Mutations of NPHS1 Gene Causing Infants with Congenital Nephrotic Syndrome: Two Chinese (Han) Cases.

出版信息

Clin Lab. 2023 Aug 1;69(8). doi: 10.7754/Clin.Lab.2023.230121.

DOI:10.7754/Clin.Lab.2023.230121

Abstract

BACKGROUND

Congenital nephrotic syndrome (CNS) of the Finnish type (CNF) is an autosomal recessively disorder. NPHS1 gene mutation is the main gene responsible for CNF. This study aimed to explore the clinical manifestations and the characteristics of genetic variation in Chinese patients with CNS.

METHODS

A 15-minute-old boy and a 34-day-old girl with CNS were included. NPHS1 gene was detected by next-generation high-throughput sequencing.

RESULTS

Patient 1 carried two novel heterozygous mutations of NPHS1 gene, one was c.204delG, p. (Leu69fs) in exon 2 of NPHS1 gene, a heterozygote frameshift mutation; the other was c.3558delT, p. (Gly1187fs) in exon 28, a heterozygote frameshift mutation. Patient 2 carried three heterozygous mutations of NPHS1, among them, c.1561-G>A. p.Asp521Asn in exon 12 is a heterozygous missense mutation. It was identified as possible de novo pathogenicity gene.

CONCLUSIONS

Three novel heterozygous mutations of NPHS1 gene were responsible for the patients with CNS and can enlarge the spectrum of NPHS1 gene mutation.

摘要

背景

芬兰型先天性肾病综合征（CNS）是一种常染色体隐性疾病。NPHS1 基因突变是导致 CNS 的主要基因。本研究旨在探讨中国 CNS 患者的临床表现和遗传变异特征。

方法

纳入 1 例 15 分钟龄的 CNS 男婴和 1 例 34 天龄的 CNS 女婴。采用下一代高通量测序检测 NPHS1 基因。

结果

患者 1 携带 NPHS1 基因的两个新的杂合突变，一个是 NPHS1 基因外显子 2 中的 c.204delG，p.（Leu69fs），杂合移码突变；另一个是外显子 28 中的 c.3558delT，p.（Gly1187fs），杂合移码突变。患者 2 携带 NPHS1 的三个杂合突变，其中 c.1561-G>A，p.Asp521Asn 位于外显子 12，为杂合错义突变。被鉴定为可能的新生致病性基因。