SLC26A3基因复合杂合突变致产前胎儿肠管扩张1例并文献复习

Fetal prenatal intestinal dilatation caused by compound-heterozygous mutations of SLC26A3 gene:A case report and literature review

目的探究SLC26A3基因突变致产前胎儿肠管扩张的临床特点及发病机制。方法回顾性分析1例产前超声诊断胎儿肠管扩张的临床资料并对SLC26A3基因突变进行文献复习。结果1名孕妇在妊娠31周时经产前超声检查发现羊水过多、胎儿肠管弥漫性扩张,遗传学基因检测发现胎儿染色体核型未见异常,全外显子组高通量测序检测结果示受检者7号染色体SLC26A3基因第3号外显子发生c.269-270dup杂合变异,第13号外显子发生c.1427del杂合变异,具有致病性,提示先天性失氯性腹泻。其中c.269-270dup为已报道的致病性变异,c.1427del为新变异,尚未有文献报道,且在神州基因数据库、人类外显子数据库(ExAC)、参考人群千人基因组(1000G)和人群基因组突变频率基因库(gnomAD)中均未发现。结论SLC26A3基因复合杂合突变可致胎儿肠管扩张,此次新发现的基因变异c.1427del补充了SLC26A3基因突变谱,为产前诊断及遗传咨询提供了更丰富的理论支持。

Objective To investigate the clinical characteristics and pathogenesis mechanism of fetal intestinal dilatation caused by SLC26A3 gene mutation.Methods The clinical data of 1 case of fetal intestinal dilatation diagnosed by prenatal ultrasound were retrospectively analyzed and the literature of SLC26A3 gene mutation was reviewed.Results Prenatal ultrasound examination of a pregnant woman at 31 weeks of gestation revealed hyperhydramnios and diffuse dilatation of the fetal intestine.Although the result of the fetal karyotype analysis was normal,the high-throughput sequencing of the whole exome revealed compound-heterozygous mutations in chromosome 7 with the heterozygous mutations c.269-270dup in exon 3 and c.1427del in exon 13.They were pathogenic and could cause the congenital chlorinated diarrhea.The mutation of c.269-270dup had been reported to be pathogenic.The c.1427del was a new mutation which had not been reported in the literature and it also had not been found in China Genome Database,Human Exon Database(ExAC),Reference Population 1000 Genome(1000G),and Population Genome Mutation Frequency Gene Bank(GnomAD).Conclusion The compound-heterozygous mutations of SLC26A3 gene can cause fetal intestinal dilatation.The novel mutation c.1427del complements the mutation spectrum of SLC26A3 gene and provides more theoretical support for prenatal diagnosis and genetic counseling.