Iranian Biomedical Journal

en Identification of Novel Mutations in the MMAA and MUT Genes among Methylmalonic Aciduria Families Molecular Genetics & Genomics Molecular Genetics & Genomics مقاله کامل Full Length/Original Article Background: Methylmalonic aciduria (MMA) 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 next generation sequencing (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. Whole exome sequencing 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. Autozygosity mapping, Genotype, Methylmalonic acidemia 397 403 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-5028-1&slc_lang=en&sid=1 Mahboobeh Jafari msjafari68@yahoo.com 0000-0002-2126-6575 No Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Fatemeh Karami fateme.karami@gmail.com 0000-0002-9590-754X No Department of Medical Genetics, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran Aria Setoodeh setoodeh@tums.ac.ir 0000-0002-7268-6473 No Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran Ali Rahmanifar Ali.rahmanifar@yahoo.com 0000-0003-2677-9270 No Clinical and Research Unit, Iranian National Society for the Study of Inborn Errors of Metabolism, Tehran, Iran Hamideh Bagherian Hamidehbagherian@yahoo.com 0000-0003-2916-1361 No Kawsar Human Genetics Research Center, Tehran, Iran Mohammad Reza Alaei dralaeimr@sbmu.ac.ir 0000-0002-9166-8166 No Department of Pediatric Endocrinology and Metabolism, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Farzaneh Rohani rohani.f@iums.ac.ir 0000-0002-2277-4862 No Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Science, Tehran, Iran Sirous Zeinali zeinali@gmail.com 0000-0002-2080-9583 Yes Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran