Artículos de revistas
Molecular basis of various forms of maple syrup urine disease in chilean patients
Fecha
2021Registro en:
Mol Genet Genomic Med. 2021;9:e1616
10.1002/mgg3.1616
Autor
Campanholi, Diana Ruffato Resende
Margutti, Ana Vitoria Barban
Silva, Wilson A.
Garcia, Daniel F.
Molfetta, Greice A.
Marques, Adriana A.
Schwartz, Ida Vanessa Döederlein
Cornejo Espinoza, Verónica del Carmen
Hamilton Viollier, Valerie
Castro Chávez, Gabriela
Sperb Ludwig, Fernanda
Borges, Ester S.
Camelo, José S
Institución
Resumen
Background Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched-chain alpha-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1 alpha, E1 beta, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients.
Methods This manuscript describes a cross-sectional study of 18 MSUD patients carried out using PCR and DNA sequencing.
Results Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients.
Conclusion If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype-phenotype relationships more efficiently.