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. 2017 Apr 7:11:17-23.
doi: 10.1016/j.ymgmr.2017.03.006. eCollection 2017 Jun.

Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi Arabian patients with maple syrup urine disease

Faiqa Imtiaz  1 , Abeer Al-Mostafa  1 , Rabab Allam  1 , Khushnooda Ramzan  1 , Nada Al-Tassan  1 , Asma I Tahir  1 , Nouf S Al-Numair  1 , Mohamed H Al-Hamed  1 , Zuhair Al-Hassnan  2   3 , Mohammad Al-Owain  2   3 , Hamad Al-Zaidan  2 , Mohammad Al-Amoudi  4 , Alya Qari  2 , Ameera Balobaid  2 , Moeenaldeen Al-Sayed  2   3
Affiliations

Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi Arabian patients with maple syrup urine disease

Faiqa Imtiaz et al. Mol Genet Metab Rep. .

Abstract

Maple syrup urine disease (MSUD), an autosomal recessive inborn error of metabolism due to defects in the branched-chain α-ketoacid dehydrogenase (BCKD) complex, is commonly observed among other inherited metabolic disorders in the kingdom of Saudi Arabia. This report presents the results of mutation analysis of three of the four genes encoding the BCKD complex in 52 biochemically diagnosed MSUD patients originating from Saudi Arabia. The 25 mutations (20 novel) detected spanned across the entire coding regions of the BCKHDA, BCKDHB and DBT genes. There were no mutations found in the DLD gene in this cohort of patients. Prediction effects, conservation and modelling of novel mutations demonstrated that all were predicted to be disease-causing. All mutations presented in a homozygous form and we did not detect the presence of a "founder" mutation in any of three genes. In addition, prenatal molecular genetic testing was successfully carried out on chorionic villus samples or amniocenteses in 10 expectant mothers with affected children with MSUD, molecularly characterized by this study.

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Figures

Fig. 1
Fig. 1
Schematic representation of known and novel mutations across BCKDHA, BCKDHB, and DBT genes identified in Saudi Arabian patients with MSUD. Novel mutations are highlighted with an asterisk (*) and closed colored circles represent all mutations and their incidence in the cohort of 52 patients.
Fig. 2
Fig. 2
Normal protein structures where the colored spheres show missense and stop codon mutation locations (a) BCKDHA (b) BCKDHB and (c) DBT mutant residues.
See this image and copyright information in PMC

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