Genetic analysis of a child with 46, XY Disorder of sex development due to a novel variant of NR5A1 gene
10.3760/cma.j.cn511374-20221210-00857
- VernacularTitle:NR5A1基因变异致46, XY性发育异常1例患者的遗传学分析
- Author:
Ailing LIU
1
;
Mingli WU
;
Ping LI
;
Haiying PENG
;
Yanyan ZHOU
;
Zengyong WANG
;
Lin LI
Author Information
1. 临沂市人民医院检验医学中心，临沂 276003
- Keywords:
Sex chromosome disorders of sex development;
NR5A1 gene;
Real-Time PCR;
Child
- From:
Chinese Journal of Medical Genetics
2024;41(2):239-243
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical features and genetic basis of a child with Disorder of sex development (DSD).Methods:A child who was admitted to the Linyi People′s Hospital for primary amenorrhoea on July 29, 2019 was selected as the study subject. Clinical data of the child was collected. Chromosomal karyotyping and quantitative real-time PCR were used to detect Y chromosome microdeletions and other chromosomal aberrations. Next-generation sequencing was carried out for the child and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 13-year-old girl, has featured primary amenorrhoea and onset of secondary sex characteristics of males. Ultrasound exam had detected no uterus and definite ovarian structure, but narrow band vaginal hypoecho and curved cavernoid structure. The child was found to have a 46, XY karyotype without an AZF deletion. DNA sequencing revealed that she has harbored a maternally derived c. 323delA (p.Q108Rfs*188) variant in the nuclear receptor subfamily 5 group A member 1 ( NR5A1) gene, which may result in a truncated protein. The variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion:The NR5A1: c. 323delA variant probably underlay the pathogenesis of 46, XY DSD in this child. The discovery of the novel variant has enriched the mutational spectrum of NR5A1 gene and provided a basis for clinical diagnosis, treatment and prenatal diagnosis.
