Shuang Hu1, Shiyue Mei, Ying Bai, Xiangdong Kong. 1. Center of Genetic and Prenatal Diagnosis, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China. kongxd@zzu.edu.cn.
Abstract
OBJECTIVE: To analyze MUT gene variants among 20 pedigrees affected with isolated methylmalonic aciduria by Sanger sequencing. METHODS: Peripheral blood samples were collected from the 20 probands and their parents. Following DNA extraction, the coding regions of the MUT gene were subjected to PCR amplification and Sanger sequencing. For 9 pedigrees, chorionic villus sampling was performed for prenatal genetic diagnosis. RESULTS: Nineteen variants were detected in the 20 pedigrees, with the most common ones including c.323G to A (p.Arg108His), c.1106G to A (p.Arg369His), c.729_730insTT(p.D244Lfs*39), and c.1107dupT (p.T370Yfs*22). Three variants were not reported previously, which included a small-scale deletion c.920_923delTCTT (p.F307Sfs*6) and two missense mutations c.419T to C (p.Leu140Pro) and 613G to A (p.Glu205Lys). For 9 pedigrees undergoing prenatal diagnosis, 1 fetus was normal, three were found to carry heterozygous mutations, while the remaining 5 fetuses have carried compound heterozygous mutations or homozygous mutations. CONCLUSION: Three novel variants of the MUT gene have been identified.
OBJECTIVE: To analyze MUT gene variants among 20 pedigrees affected with isolated methylmalonic aciduria by Sanger sequencing. METHODS: Peripheral blood samples were collected from the 20 probands and their parents. Following DNA extraction, the coding regions of the MUT gene were subjected to PCR amplification and Sanger sequencing. For 9 pedigrees, chorionic villus sampling was performed for prenatal genetic diagnosis. RESULTS: Nineteen variants were detected in the 20 pedigrees, with the most common ones including c.323G to A (p.Arg108His), c.1106G to A (p.Arg369His), c.729_730insTT(p.D244Lfs*39), and c.1107dupT (p.T370Yfs*22). Three variants were not reported previously, which included a small-scale deletion c.920_923delTCTT (p.F307Sfs*6) and two missense mutations c.419T to C (p.Leu140Pro) and 613G to A (p.Glu205Lys). For 9 pedigrees undergoing prenatal diagnosis, 1 fetus was normal, three were found to carry heterozygous mutations, while the remaining 5 fetuses have carried compound heterozygous mutations or homozygous mutations. CONCLUSION: Three novel variants of the MUT gene have been identified.