Identification of Novel Mutations in the MMAA and MUT Genes among Methylmalonic Aciduria Families.

Q2 Biochemistry, Genetics and Molecular Biology Iranian Biomedical Journal Pub Date : 2023-02-12 DOI:10.61186/ibj.3782

Mahboobeh Jafari, Fatemeh Karami, Aria Setoodeh, Ali Rahmanifar, Hamideh Bagherian, Mohammad Reza Alaei, Farzaneh Rohani, Sirous Zeinali

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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.

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甲基丙二酸尿症家族中 MMAA 和 MUT 基因新突变的鉴定

背景：甲基丙二酸尿症是一种罕见的常染色体隐性遗传代谢性疾病。目前仍有一些甲基丙二酸尿症患者的致病基因未发现突变。本研究旨在利用自交系图谱和 NGS 方法确定伊朗 MMA 家族中的基因突变：方法：使用 MUT、MMAA 和 MMAB 基因侧翼的 19 个 STR 标记，对从 12 名无亲属关系的 MMA 患者及其家庭成员分离的 DNA 进行多重 PCR，然后进行 Sanger 测序。对没有突变的患者进行了 WES 分析：结果：单体型分析和 Sanger 测序显示，MMAA 和 MUT 基因中分别存在 A252Vf*5 和 G87R 两种新型突变。三名患者在自交系图谱或 NGS 分析中均未发现突变：结论：MUT 基因第 2 和第 3 外显子以及 MMAB 基因第 7 外显子中的高频突变与全球 MMA 患者基因变异的预期频率一致。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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