Genetic analysis and prenatal diagnosis of novel GCDH variant responsible for glutaric aciduria type Ⅰ

Abstract

Objective To identify pathogenic gene variants of glutaric aciduria typeⅠ (GAⅠ) and provide reference for prenatal diagnosis of this disease. Methods Genomic DNA was extracted from the family members of a suspected case of GAⅠ. Whole exome sequencing was performed on the proband, and DNA Sanger sequencing was performed on the parents to verify the variants and analyze their pathogenicity. Amniotic fluid fetal cells were extracted by amniocentesis at 18 weeks of gestation to detect GCDH gene. Literature review was conducted from PubMed, CNKI, Wanfang Data and Chongqing VIP databases using the keywords of “glutaric aciduria typeⅠ”, “GCDH” and prenatal diagnosis in both Chinese and English. Results Two variants of GCDH gene were detected in the proband： c.206_207delAC(p.Thr70Leufs*117) and c.892G>A(p.Ala298Thr), from the father and mother, respectively. The paternal variant was a novel variant, and the maternal variant was a known variant. And two variants were both pathogenic. GCDH gene variant analysis of amniotic fluid fetal cells showed compound heterozygous c.206_207delAC and c.892G>A variants. The couple decided to terminate the pregnancy thereafter. A total of 9 families with prenatal diagnosis of GAⅠ were retrieved by GCDH gene sequencing analysis. Among them, 5 fetuses from 4 families had prenatal diagnosis of GAⅠ. Four families decided to terminate the pregnancy, and only 1 family insisted on continuing pregnancy until full-term delivery. Conclusions The novel variant of GCDH gene (c.206_207delAC) is detected in this family of GAⅠ. The pathogenic variant sites of GCDH gene are identified in the proband of this GAⅠ family.

Keywords

• |glutaric aciduria type i|gcdh gene|novel variant|prenatal diagnosis