Identification of six novel mutations in Iranian patients with maple syrup urine disease and their in silico analysis​

Mutation Research
Maryam Abiri Sirous Zeinali

Abstract

Maple syrup urine disease (MSUD) is a rare inborn error of branched-chain amino acid metabolism. The disease prevalence is higher in populations with elevated rate of consanguineous marriages such as Iran. Different types of disease causing mutations have been previously reported in BCKDHA, BCKDHB, DBT and DLD genes known to be responsible for MSUD phenotype. In this study, two sets of multiplex polymorphic STR (Short Tandem Repeat) markers linked to the above genes were used to aid in homozygosity mapping in order to find probable pathogenic change(s) in the studied families. The families who showed homozygote haplotype for the BCKDHA gene were subsequently sequenced. Our findings showed that exons 2, 4 and 6 contain most of the mutations which are novel. The changes include two single nucleotide deletion (i.e. c. 143delT and c.702delT), one gross deletion covering the whole exon four c.(375+1_376-1)_(8849+1_885-1), two splice site changes (c.1167+1G>T, c. 288+1G>A), and one point mutation (c.731G>A). Computational approaches were used to analyze these two novel mutations in terms of their impact on protein structure. Computational structural modeling indicated that these mutations might affect structural stability and multime...Continue Reading

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Citations

Oct 12, 2016·Journal of Nutritional Science and Vitaminology·Katsumi Shibata, Momoka Sakamoto
Jan 8, 2018·Journal of Pediatric Endocrinology & Metabolism : JPEM·Monica ZeynalzadehMohammad Reza Abbaszadegan
Nov 3, 2020·Orphanet Journal of Rare Diseases·Ana Vitoria Barban MarguttiJosé Simon Camelo

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