Two novel mutations in the BCKDHB gene (R170H, Q346R) cause the classic form of maple syrup urine disease (MSUD)

Analysis of gene mutations in Chinese patients with maple syrup urine disease

“…Five mutations in the BCKDHA gene have been reported in 3 Korean patients [10] and one mutation in a single Thai patient [11]. However, there are only three articles describing two mutations in the BCKDHA gene [12] and two in the BCKDHB gene [13] in China, despite the huge population. In this study, we screened the BCKDHA, BCKDHB and DBT genes in 16 patients.…”

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

“…E1 protein consisted of α2β2 heterotetramer was a ThDP‐dependent enzyme . The structural stabilization of this component of the BCKD complex was depended on the ThDP cofactors that bound to the two active sites at the α‐β’ and α’‐β interfaces, and presence of K + ions . Therefore, the precise spatial correlations of E1 component, including the ThDP‐binding domain and K + ion‐binding site, are critical to the enzymatic function of E1 component .…”

“…18,19 The structural stabilization of this component of the BCKD complex was depended on the ThDP cofactors that bound to the two active sites at the α-β' and α'-β interfaces, and presence of K + ions. 20 Therefore, the precise spatial correlations of E1 component, including the ThDP-binding domain and K + ion-binding site, are critical to the enzymatic function of E1 component. 15,21 S184 residue was located in a β-strand associated with the K + ion-binding pocket and belonged to ThDP-binding domain.…”

Alu-miRNA interactions modulate transcript isoform diversity in stress response and reveal signatures of positive selection

“…Genes like GFOD2 and ANO8 , wherein the derived allele is nearing fixation in CEU and CHB, are known to be under selection pressure with GFOD2 associated with diet induced changes in blood lipid of the Mexican population4950. Similarly, mutations in BCKDHB gene (high DAF in CEU & CHB) are linked to cases of maple syrup urine disease, only in the Chinese and Korean populations51. Moreover, other genes related to DNA damage response/apoptosis ( GINS1, ICMT, TLK2, CRTAM, DNAJB7 and TNFRSF9 ), cell shape/integrity ( TBCCD1, BVES and GUCDI) and neuro-protection ( NMNAT1 ) also show signatures of positive selection for Alu-miRNA targets52.…”