Genetic analysis and prenatal diagnosis of a pedigree with methylmalonic acidemia

VernacularTitle:1个甲基丙二酸血症家系的遗传学分析及产前诊断
Author: Xiaoxi HUO ¹ ; Wen JIANG ; Ye JIN ; Wenjing ZHANG ; Tong DONG ; Yang LIU ; Yanping LU
Author Information

1. 中国人民解放军总医院第七医学中心妇产医学部，北京　100700
Keywords: Amino acid metabolism, inborn errors; Methylmalonyl-CoA mutase; Genetic variation; Prenatal diagnosis; Whole exome sequencing
From: Chinese Journal of Perinatal Medicine 2023;26(11):960-963
CountryChina
Language:Chinese
Abstract: This article reports a pedigree with two previously deceased neonates. Both neonates did not experience asphyxia but passed away on their 5th and 13th day of life. The chromosomal analysis of the parents' karyotype revealed no abnormalities. Clinical manifestations of the two deceased cases and relevant medical records were recollected. Whole exome sequencing was conducted on the stem blood sample of Neonate 2, revealing a c.729_730insTT homozygous mutation (p.D244Lfs*39) in the methylmalonyl-CoA mutase gene (NM_000255). It was confirmed that Neonate 2 was affected with methylmalonic acidemia. Amniocentesis was performed at 20 +3 weeks in the current pregnancy. Sanger sequencing of amniotic fluid indicated that the fetus carried the same gene mutation as Neonate 2. Consequently, the fetus was expected to be a patient with methylmalonic acidemia and to exhibit the same phenotype as Neonate 2. Termination of pregnancy, therefore, was selected at 24 weeks of gestation.