Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease

Abstract

Background Maple sirup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder. The disease‐causing mutations can affect the BCKDHA , BCKDHB , and DBT genes encoding for the E1α, E1β, and E2 subunits of the multienzyme branched‐chain α‐keto acid dehydrogenase (BCKDH) complex. In the present study, novel pathogenic variants in BCKDHB and DBT genes were identified in three Vietnamese families with MSUD. Methods Three newborn patients from three unrelated Vietnamese families were diagnosed with MSUD at the Metabolic Clinic, National Hospital of Pediatrics. Blood samples of 11 relatives from two generations of the three families diagnosed with MSUD were analyzed using exome and Sanger sequencing analyses. Results Novel pathogenic variants in BCKDHB (c.1103C>T, c.989A>G, and c.704G>A), and DBT (c.263_265delAAG) genes were identified in three pediatric patients with MSUD. Conclusions We have identified novel pathogenic variants in the MSUD‐related genes in the pedigree of the three patient's families. Our findings expand the mutational spectrum of MSUD and provide the scientific basis for genetic counseling for the patient's families.

Identification of gene mutations in six Chinese patients with maple syrup urine disease

“…The human BCKDHB gene is located at 6q14.1, which contains 10 exons and 9 introns with a full length of 239 kb and encodes 392 amino acids. Patients with BCKDHA and BCKDHB gene mutations tend to have a Classic MUSD clinical manifestation (Nguyen et al, 2020;Jiang et al, 2021). E2 is encoded by the DBT (OMIM 248610) gene.…”

“…The full length of PPM1K is 26 kb long and encodes 372 amino acids. PPM1K encodes mitochondrial protein phosphatase that also causes MSUD when gene mutated (Nguyen et al, 2020). As of February 2022, the HGMD database (http://www.…”