Hereditary characteristics of the S339L mutation in a patient with maple syrup urine disease in Vietnam
Author affiliations
DOI:
https://doi.org/10.15625/2615-9023/v42n2.14913Keywords:
BCKAD, BCKDHB, MSUD, S339L, whole exome sequencing.Abstract
Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by malfunction of the branched-chain α-ketoacid dehydrogenase complex (BCKDH). This enzyme complex participates in the catalyzing metabolisms of the branched-chain α-ketoacids, the second step of the degradation of branched-chain amino acids. Impaired activities of the BCKAD complex lead to an increase of the levels of branched- chain amino acid such as leucine, valine, and isoleucine in the blood. In children with maple syrup urine disease, catalysis of the metabolisms of some amino acids failed to be implemented, leading to an accumulation of the amino acids which has been shown as one of the causes of neurological complications, intellectual disabilities, and nervous paralysis or even death. Pathogenic mutations normally occur in BCKDHA, BCKDHB, DBT and DLD genes which encode the E1α, E1β, and E2 subunits of the BCKDH complex. In the present study, a homozygous mutation in the BCKDHB gene (c. 1016C>T) in a pediatric patient with MSUD diagnosed at The National Hospital of Pediatrics was identified using whole exome and Sanger sequencing methods. As a result, the inheritance of the homozygous mutation related to MSUD in BCKDHB gene within the pedigree of the patient’s family was determined. The results indicated that the mutation in the BCKDHB gene was inherited from both of the patient’s parents. In addition, this finding provides an important scientific basis to researches on MSUD in the Vietnamese population.
Downloads
Metrics
References
Ali E. Z., Ngu L. H., 2018. Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease (MSUD) in Malaysian population. Mol. Genet. Metab. Ref., 17: 22−30.
Bashyam M. D., Chaudhary A. K., Sinha M., Nagarajaram H. A., Devi A. R. R., Bashyam L., Reddy E., Dalal A., 2012. Molecular genetic analysis of MSUD from India reveals mutations causing altered protein truncation affecting the C-termini of E1α and E1β. J. Cell Biochem., 113(10): 3122−3132.
Blackburn P. R., Gass J. M., Pinto E., Vairo F., Farnham K. M., Atwal H. K., Macklin S., Klee E., Atwal P. S., 2017. Maple syrup urine disease: mechanisms and management. Appl. Clin. Genet., 10: 57−66.
Deepti G., Sunita B. M., Renu S., Sudha K., Ratna D. P., Jyotsna V., Thomas E., Yosuke S., Seiji Y., Roumi D., Ishwar C. V., 2015. Identification of mutations, genotype-phenotype correlation and prenatal diagnosis of maple syrup urine disease in Indian patients. Eur. J. Med. Genet., 58: 471–478.
Guo Y., Liming L., Jiang L., 2015. Two novel compound heterozygous mutations in the BCKDHB gene that cause the intermittent form of maple syrup urine disease. Metab. Brain Dis., 30(6): 1395−1400.
Jaafar N., Moleirinho A., Kerkeni E., Monastiri K., Seboui H., Amorim A., Prata M., Quental S., 2013. Molecular characterization of maple syrup urine disease patients from Tunisia. Gene, 517(1): 116−119.
Kerstin G., Ali D., Turgay C., Serap H. K. S., Gülden F. G., Mübeccel D., Oliver F., Udo W., 2009. Molecular genetics of maple syrup urine disease in the Turkish population. Turk. J. Pediatr., 51: 97−102.
Lee J. Y., Chiong M. A., Estrada S. C., Cutiongco-De La Paz E. M., Silao C. L. T., Padilla C. D., 2008. Maple syrup urine disease (MSUD) - Clinical profile of 47 Filipino patients. J. Inherit. Metab. Dis., 31 (Suppl.2).
Nellis M. M., Danner D. J., 2001. Gene preference in maple syrup urine disease. Am. J. Hum. Genet., 68: 232−237.
Skvorak K. J., 2009. Animal models of maple syrup urine disease. J. Inherit. Metab. Dis., 229−246.
Theodoros G., Jacinta L. C., Max W. R., Goula S., Mark K., David T. C., Anthi D., 2009. Maple syrup urine disease in Cypriot families: identification of three novel mutations and biochemical characterization of the p.Thr211Met mutation in the E1alpha subunit. Genet. Test Mol. Biomark., 13: 657−664.
Wynn R. M., Chuang J. L., Sansaricq C., Mandel H., Chuang D. T., 2001. Biochemical basis of type Ib (E1β) mutations in maple syrup urine disease. A prevalent allele in patients from the druze kindred in Israel. J. Biol. Chem., 276(39): 36550–36556.
Zhang B., Kuntz M. J., Goodwin G. W., Edenberg H. J., Crabb D. W., Harris., Ramzan H. K., 1989. cDNA cloning of the E1 alpha subunit of the branched chain alpha-keto acid dehydrogenase and elucidation of a molecular basis for maple syrup urine disease. Ann. NY Acad. Sci., 573: 130−136.
Downloads
Published
How to Cite
Issue
Section
