Identification of a novel homozygous mutation (S144I) in a Malay patient with maple syrup urine disease

Ali, Ernie Zuraida; Yunus, Zabedah Md; Desa, Norsiah Md; Ngu, Lock Hock

doi:10.1515/jpem-2012-0424

Cited by 3 publications

(2 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To the best of our knowledge, only one mutation in patients with MSUD has been reported in Malaysia [ 23 ]. Here, we presented the first comprehensive study of MSUD mutational spectrum for Malaysia population.…”

Section: Discussionmentioning

confidence: 99%

Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population

Ali

Ngu

2018

Molecular Genetics and Metabolism Reports

Self Cite

View full text Add to dashboard Cite

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder. This disorder is usually caused by mutations in any one of the genes; BCKDHA, BCKDHB and DBT, which represent E1α, E1β and E2 subunits of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, respectively. This study presents the molecular characterization of 31 MSUD patients. Twenty one mutations including 14 new mutations were identified. The BCKDHB gene was the most commonly affected (45.2%) compared to BCKDHA gene (16.1%) and DBT gene (38.7%). In silico webservers predicted all mutations were disease-causing. In addition, structural evaluation disclosed that all new missenses in BCKDHA, BCKDHB and DBT genes affected stability and formation of E1 and E2 subunits. Majority of the patients had neonatal onset MSUD (26 of 31). Meanwhile, the new mutation; c.1196C > G (p.S399C) in DBT gene was noted to be recurrent and found in 9 patients. Conclusion: Our findings have expanded the mutational spectrum of the MSUD and revealed the genetic heterogeneity among Malaysian MSUD patients. We also discovered the p.S399C from DBT gene was noted as a recurrent mutation in Malay community and it suggested the existence of common and unique mutation in Malay population.

show abstract

Section: Discussionmentioning

confidence: 99%

Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population

Ali

Ngu

2018

Molecular Genetics and Metabolism Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, the Mutationtaster program and PDB databases were used to analyze the pathogenicity of the novel mutation. Bioinformatics can be used as a good approach to analyze the effect of novel mutations on protein function if there was no direct evidence to show the pathogenicity of mutations . The combination of clinical data, in silico prediction, and crystal structure analysis has the capacity for providing reliable and timely information on the effects of novel mutations on protein function and clinical phenotypes in patient with MSUD.…”

Section: Discussionmentioning

confidence: 99%

Silico analysis of a novel mutation c.550delT in a Chinese patient with maple syrup urine disease

Meng

Wang

et al. 2018

Clinical Case Reports

View full text Add to dashboard Cite

show abstract

A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)

Miryounesi

Ghafouri‐Fard

Goodarzi

et al. 2015

Journal of Pediatric Endocrinology and Metabolism

View full text Add to dashboard Cite

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disease caused by mutations in the BCKDHA, BCKDHB, DBT and DLD genes, which encode the E1α, E1β, E2 and E3 subunits of the branched chain α ketoacid dehydrogenase (BCKD) complex, respectively. This complex is involved in the metabolism of branched-chain amino acids. In this study, we analyzed the DNA sequences of BCKDHA and BCKDHB genes in an infant who suffered from MSUD and died at the age of 6 months. We found a new missense mutation in exon 5 of BCKDHB gene (c.508C>T). The heterozygosity of the parents for the mentioned nucleotide change was confirmed by direct sequence analysis of the corresponding segment. Another missense mutation has been found in the same codon previously and shown by in silico analyses to be deleterious. This report provides further evidence that this amino acid change can cause classic MSUD.

show abstract

Identification of a novel homozygous mutation (S144I) in a Malay patient with maple syrup urine disease

Cited by 3 publications

References 4 publications

Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population

Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population

Silico analysis of a novel mutation c.550delT in a Chinese patient with maple syrup urine disease

A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)

Contact Info

Product

Resources

About