Maple Syrup Urine Disease in Cypriot Families: Identification of Three Novel Mutations and Biochemical Characterization of the p.Thr211Met Mutation in the E1α Subunit

Georgiou, Theodoros; Chuang, Jacinta L.; Wynn, R. Max; Stylianidou, Goula; Korson, Mark S.; Chuang, David T.; Drousiotou, Anthi

doi:10.1089/gtmb.2009.0065

Cited by 9 publications

(9 citation statements)

References 23 publications

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“…Twenty of the mutations were novel and 5 mutations had already previously identified [16], [17], [18], [19], [20]. As a whole, 15 mutations were missense, 4 resulted in frameshift, 3 were nonsense and 3 affected splicing.…”

Section: Resultsmentioning

confidence: 99%

“…Direct sequencing in both the forward and reverse directions in 52 MSUD patients identified a total of 25 different homozygous mutations ( Table 1 ); 9 mutations in BCKDHA , 10 mutations in BCKDHB , and 6 mutations in the DBT gene. Twenty of the mutations were novel and 5 mutations had already previously identified [16] , [17] , [18] , [19] , [20] . As a whole, 15 mutations were missense, 4 resulted in frameshift, 3 were nonsense and 3 affected splicing.…”

Section: Resultsmentioning

confidence: 99%

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

Imtiaz

Al-Mostafa

Allam

et al. 2017

Molecular Genetics and Metabolism Reports

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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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Imtiaz

Al-Mostafa

Allam

et al. 2017

Molecular Genetics and Metabolism Reports

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“…MSUD is a disorder of branched‐chain amino acid metabolism caused by mutations in any gene encoding the BCKD complex. There are approximately 29% of mutations occurring in the BCKDHB gene . In this study, compound heterozygous mutations c.1046G>A and c.550delT in the BCKDHB gene had been detected in this patient.…”

Section: Discussionmentioning

confidence: 49%

“…There are approximately 29% of mutations occurring in the BCKDHB gene. 16,17 In this study, compound heterozygous mutations c.1046G>A and c.550delT in the BCKDHB gene had been detected in this patient. Her parents were each heterozygous for one of these mutation, demonstrating that these two mutations were parentally inherited.…”

Section: Discussionmentioning

confidence: 52%

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

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“…Gly→Ala DLD gene variants account for 13% 13 . Each gene has high allelic heterogeneity, with the exception of gene mutation hotspots found in minority of ethnic groups, such as the most common mutation in the Mennonite community being the BCKDHA gene c.1312T>A (p.Tyr393Asn) 14 , Portuguese gypsy mutation hotspot c.117delC 15 .…”

Section: Gly→arg Ser→pro Lys→thrmentioning

confidence: 99%

Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease

Fang¹,

Zhu²,

Yin³

et al. 2021

Preprint

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Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 girls and 4 boys) with MSUD from 8 unrelated Chinese families were diagnosed at the age of 9 days to 1 year and 8 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT, DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene，10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter，p.Arg111Ter，p.S184Pfs*46, p.Arg170Cys, p.I160Ffs*25) in BCKDHB gene, 1 variants (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were found. NGS plus Sanger sequencing detection is effective and accurate for making gene diagnosis. Computational structural modeling indicated that these novel variations might affect structural stability.

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Maple Syrup Urine Disease in Cypriot Families: Identification of Three Novel Mutations and Biochemical Characterization of the p.Thr211Met Mutation in the E1α Subunit

Cited by 9 publications

References 23 publications

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

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

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

Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease

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