Clinical Genetics
Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency
Chen Jia, Yuan Huizhen, Xie Kang, Guo Zhen, Yang Yan, Zou Yongyi, Chen Ge, Liu Yanqiu
Published 2020-12-10
Cite as Chin J Med Genet, 2020, 37(12): 1360-1363. DOI: 10.3760/cma.j.cn511374-20200203-00055
Abstract
ObjectiveTo explore the genetic basis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency.
MethodsTrio whole exome sequencing (WES) was carried out for the pedigree. Pathogenicity of the identified variant was predicted based on the latest recommendation of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided for subsequent pregnancy through Sanger sequencing.
ResultsTrio WES showed that the proband has carried compound heterozygous c. 68delG and c. 796G>C variants ofNAGS gene, for which the mother and father were respectively heterozygous carriers.Neither variant was reported previously. Based on the ACMG guidelines, the c. 68delG variant was classified as "likely pathogenic" (PVS1+ PM2), while the c. 796G>C variant was classified as with "uncertain significance" (PM2+ BP4). Sanger sequencing validated the above findings, and only detected the heterozygous c. 796G>C variant in the amniotic fluid sample. The fetus was followed up till 6 month after birth with no obvious abnormality.
ConclusionThe compound heterozygous c. 68delG and c. 796G>Cvariants of theNAGS gene probably underlay the disorder in this pedigree, and the resulth asenabled genetic counseling and prenatal diagnosis for this pedigree.
Key words:
N-acetylglutamate synthase deficiency; Hyperammonemia; Urea cycle disorder; NAGS gene; Prenatal diagnosis
Contributor Information
Chen Jia
Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China
Yuan Huizhen
Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China
Xie Kang
Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China
Guo Zhen
Department of Ultrasonography, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China
Yang Yan
Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China
Zou Yongyi
Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China
Chen Ge
Central Laboratory, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China
Liu Yanqiu
Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China
