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

Abiri, Maryam; Karamzadeh, Razieh; Karimipoor, Morteza; Ghadami, Shirin; Alaei, Mohammad Reza; Bagheri, Samira Dabagh; Bagherian, Hamideh; Setoodeh, Aria; Noori–Daloii, Mohammad Reza; Zeinali, Sirous

doi:10.1016/j.mrfmmm.2016.01.005

Cited by 18 publications

(21 citation statements)

References 29 publications

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“…Therefore, the administration of B-group vitamins is better for the improvement of branched-chain amino acid degradation than that of only vitamin B1. Recently, novel mutations of BCKDC and the related enzyme genes associated with MSUD have been reported (22,23). The participants belonging to the upper tertile in the present experiment might have minor gene mutations of BCKDC and the related genes.…”

Section: Discussionmentioning

confidence: 70%

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

Shibata

Sakamoto

2016

J Nutr Sci Vitaminol

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SummaryTo find a functional biomarker of B-group vitamins, we collected 24-h urine samples from young Japanese women who lived in the community (n529) to measure branched-chain 2-oxo acids such as 2-oxo-3-methylbutanoic acid, 2-oxo-3-methylpentanoic acid, and 2-oxo-4-methylpentanoic acid because B-group vitamins are involved in the catabolism of branched-chain amino acids. The relationships between each pair of the three urinary 2-oxo acids were very high (2-oxo-3-methylbutanoic acid and 2-oxo-3-methylpentanoic acid, p,0.001; 2-oxo-3-methylbutanoic acid and 2-oxo-4-methylpentanoic acid, p,0.001; 2-oxo-3-methylpentanoic acid and 2-oxo-4-methylpentanoic acid, p,0.001). The participants were divided into three groups using the upper (n510), middle (n59), and lower tertiles (n510) based on the urinary excretion amounts of the sum of the three branchedchain 2-oxo acids. The administration of capsules containing the daily necessary amounts of B-group vitamins led to a decrease in the urinary excretion of the sum of the three types of branched-chain 2-oxo acids in participants belonging to the upper tertile. A similar phenomenon was observed in the middle tertile, but not in the lower tertile. Intakes of B-group vitamins and the urinary excretion amounts of B-group vitamins were not observed to be significantly different among the upper, middle, and lower tertiles. These results indicate that some young Japanese women need much higher levels of B-group vitamins than the Dietary Reference Intakes for Japanese. Thus, urinary branched-chain 2-oxo acids are useful functional biomarkers for B-group vitamins in humans.

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Section: Discussionmentioning

confidence: 70%

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

Shibata

Sakamoto

2016

J Nutr Sci Vitaminol

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“…Based on clinical presentation onset age and residual BCKD complex activity, MUSD can be divided into five forms: classic, intermediate, intermittent, thiamine responsive, and E3 deficient . Approximately 75% of affected individuals has the classic form with less than 2% residual BCKD complex activity and exhibits the most serious phenotype.…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 75% of affected individuals has the classic form with less than 2% residual BCKD complex activity and exhibits the most serious phenotype. Generally, patients with classic MSUD appear normal at birth but show poor feeding and lethargy within a week followed by more severe symptoms such as convulsions and progressive brain damage . If untreated, this condition is fatal and most patients often die .…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8] Based on clinical presentation onset age and residual BCKD complex activity, MUSD can be divided into five forms: classic, intermediate, intermittent, thiamine responsive, and E3 deficient. 9,10 Approximately 75% of affected individuals has the classic form with less than 2% residual BCKD complex activity and exhibits the most serious phenotype. Generally, patients with classic MSUD appear normal at birth but show poor feeding and lethargy within a week followed by more severe symptoms such as convulsions and progressive brain damage.…”

Section: Introductionmentioning

confidence: 99%

“…Generally, patients with classic MSUD appear normal at birth but show poor feeding and lethargy within a week followed by more severe symptoms such as convulsions and progressive brain damage. 6,9,11,12 If untreated, this condition is fatal and most patients often die. 13 Therefore, an early diagnosis and a timely treatment of MSUD patients are crucial to their better prognosis.…”

Section: Introductionmentioning

confidence: 99%

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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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Clinical characteristics and mutation analysis of five Chinese patients with maple syrup urine disease

Yang

Gao

et al. 2018

Metab Brain Dis

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Maple syrup urine disease (MSUD) is an autosomal recessive disorder affecting branched-chain amino acids (BCAAs) metabolism and caused by a defect in the thiamine-dependent enzyme branched chain α-ketoacid dehydrogenase (BCKD) with subsequent accumulation of BCAAs and corresponding branched-chain keto acids (BCKAs) metabolites. Presently, at least 4 genes of BCKDHA, BCKDHB, DLD and DBT have been reported to cause MSUD. Furthermore, more than 265 mutations have been identified as the cause across different populations worldwide. Some studies have reported the data of gene mutations in Chinese people with MSUD. In this study, we present clinical characteristics and mutational analyses in five Chinese Han child with MSUD, which had been screened out by tandem mass spectrometry detection of amino acids in blood samples. High-throughput sequencing, Sanger sequence and real-time qualitative PCR were performed to detect and verify the genetic mutations. Six different novel genetic variants were validated in BCKDHB gene and BCKDHA gene, including c.523 T > C, c.659delA, c.550delT, c.863G > A and two gross deletions. Interestingly, 3 cases had identical mutation of BCKDHB gene (c.659delA). We predicted the pathogenicity and analyzed the clinical characteristics. The identification of these mutations in this study further expands the mutation spectrum of MSUD and contributes to prenatal molecular diagnosis of MSUD.

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

Cited by 18 publications

References 29 publications

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

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

Clinical characteristics and mutation analysis of five Chinese patients with maple syrup urine disease

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

Cited by 18 publications

References 29 publications

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

Urinary Branched-Chain 2-Oxo Acids as a Biomarker for Function of B-Group Vitamins in Humans

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

Clinical characteristics and mutation analysis of five Chinese patients with maple syrup urine disease

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Product

Resources

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