Identification of Novel Mutations in the Mmaa and Mut Genes Among Methylmalonic Aciduria Families Publisher Pubmed



Jafari M¹ ; Karami F² ; Setoodeh A³ ; Rahmanifar A⁴ ; Bagherian H⁵ ; Alaei MR⁶ ; Rohani F⁷ ; Zeinali S⁸ Show Affiliations
Source: Iranian Biomedical Journal Published:2023

Abstract

Background: Methylmalonic aciduria is a rare inherited metabolic disorder with autosomal recessive inheritance pattern. There are still MMA patients without known mutations in the responsible genes. This study aimed to identify mutations in Iranian MMA families using autozygosity mapping and NGS. Methods: Multiplex PCR was performed on DNAs isolated from 12 unrelated MMA patients and their family members using 19 STR markers flanking MUT, MMAA, and MMAB genes, followed by Sanger sequencing. WES was carried out in the patients with no mutation. Results: Haplotype analysis and Sanger sequencing revealed two novel, mutations, A252Vf*5 and G87R, within the MMAA and MUT genes, respectively. Three patients showed no mutations in either autozygosity mapping or NGS analysis. Conclusion: High-frequency mutations within exons 2 and 3 of MUT gene and exon 7 of MMAB gene are consistent with the global expected frequency of genetic variations among MMA patients. © 2023, Pasteur Institute of Iran. All rights reserved.