Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease
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Monica Zeynalzadeh
Abstract
Background:
Maple syrup urine disease (MSUD) is a rare metabolic autosomal recessive disorder caused by dysfunction of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex. Mutations in the BCKDHA, BCKDHB and DBT genes are responsible for MSUD. The current study analyzed seven Iranian MSUD patients genetically and explored probable correlations between their genotype and phenotype.
Methods:
The panel of genes, including BCKDHA, BCKDHB and DBT, was evaluated, using routine the polymerase chain reaction (PCR)-sequencing method. In addition, protein modeling (homology and threading modeling) of the deduced novel mutations was performed. The resulting structures were then analyzed, using state-of-the-art bioinformatics tools to better understand the structural and functional effects caused by mutations.
Results:
Seven mutations were detected in seven patients, including four novel pathogenic mutations in BCKDHA (c.1198delA, c.629C>T), BCKDHB (c.652C>T) and DBT (c.1150A>G) genes. Molecular modeling of the novel mutations revealed clear changes in the molecular energy levels and stereochemical traits of the modeled proteins, which may be indicative of strong correlations with the functional modifications of the genes. Structural deficiencies were compatible with the observed phenotypes.
Conclusions:
Any type of MSUD can show heterogeneous clinical manifestations in different ethnic groups. Comprehensive molecular investigations would be necessary for differential diagnosis.
Acknowledgments
The authors would like to thank the patients and their families who participated in this study. The results of this study were part of an MD student thesis.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was supported by the grant number 921391 from the Vice Chancellor for Research at MUMS.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- The role of corticosteroid-binding globulin in the evaluation of adrenal insufficiency
- Original Articles
- Association of sodium intake with insulin resistance in Korean children and adolescents: the Korea National Health and Nutrition Examination Survey 2010
- Decrease in serum chemerin through aerobic exercise plus dieting and its association with mitigation of cardio-metabolic risk in obese female adolescents
- Ultrasonographic assessment of pubertal breast development in obese children: compliance with the clinic
- Associations of leptin, insulin and lipids with retinal microvasculature in children and adolescents
- Association of cord blood ghrelin, leptin and insulin concentrations in term newborns with anthropometric parameters at birth
- Management of thyrotoxicosis in children and adolescents: 35 years’ experience in 304 patients
- Clinical and cytogenetic features of 516 patients with suspected Turner syndrome – a single-center experience
- Response to growth hormone treatment in very young patients with growth hormone deficiencies and mini-puberty
- Reference centile curves for wrist circumference for Indian children aged 3–18 years
- Comparison between two inhibin B ELISA assays in 46,XY testicular disorders of sex development (DSD) with normal testosterone secretion
- Genetic mutations associated with neonatal diabetes mellitus in Omani patients
- Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease
- Improved medical-alert ID ownership and utilization in youth with congenital adrenal hyperplasia following a parent educational intervention
- Letter to the Editor
- Identification of five mutations in a patient with galactose metabolic disorders
- Case Reports
- Partial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor
- Vaginal bleeding and a giant ovarian cyst in an infant with 21-hydroxylase deficiency
- Insulin-mediated pseudoacromegaly: a report of two pediatric patients
- Novel compound heterozygous variants in the LHCGR gene identified in a subject with Leydig cell hypoplasia type 1
Artikel in diesem Heft
- Frontmatter
- Review
- The role of corticosteroid-binding globulin in the evaluation of adrenal insufficiency
- Original Articles
- Association of sodium intake with insulin resistance in Korean children and adolescents: the Korea National Health and Nutrition Examination Survey 2010
- Decrease in serum chemerin through aerobic exercise plus dieting and its association with mitigation of cardio-metabolic risk in obese female adolescents
- Ultrasonographic assessment of pubertal breast development in obese children: compliance with the clinic
- Associations of leptin, insulin and lipids with retinal microvasculature in children and adolescents
- Association of cord blood ghrelin, leptin and insulin concentrations in term newborns with anthropometric parameters at birth
- Management of thyrotoxicosis in children and adolescents: 35 years’ experience in 304 patients
- Clinical and cytogenetic features of 516 patients with suspected Turner syndrome – a single-center experience
- Response to growth hormone treatment in very young patients with growth hormone deficiencies and mini-puberty
- Reference centile curves for wrist circumference for Indian children aged 3–18 years
- Comparison between two inhibin B ELISA assays in 46,XY testicular disorders of sex development (DSD) with normal testosterone secretion
- Genetic mutations associated with neonatal diabetes mellitus in Omani patients
- Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease
- Improved medical-alert ID ownership and utilization in youth with congenital adrenal hyperplasia following a parent educational intervention
- Letter to the Editor
- Identification of five mutations in a patient with galactose metabolic disorders
- Case Reports
- Partial androgen insensitivity syndrome due to somatic mosaicism of the androgen receptor
- Vaginal bleeding and a giant ovarian cyst in an infant with 21-hydroxylase deficiency
- Insulin-mediated pseudoacromegaly: a report of two pediatric patients
- Novel compound heterozygous variants in the LHCGR gene identified in a subject with Leydig cell hypoplasia type 1
