ClinVar

In a survey of 204 individuals with methylmalonic aciduria and homocystinuria cblC type (MAHCC; 277400), Lerner-Ellis et al. (2006) found 34 examples of the 394C-T mutant allele of the MMACHC gene, predicted to result in an arg132-to-ter mutation (R132X). The R132X mutation was primarily associated with late-onset disease and was noted in the homozygous state among published individuals in Asiatic-Indian, Pakistani, or Middle Eastern descent and reported by Morel et al. (2006) in an additional 9 unpublished patients from their database who were either of Asiatic-Indian, Pakistani, or Middle Eastern descent.

Ben-Omran et al. (2007) reported 2 unrelated girls of Pakistani and Bengali origin, respectively, with cblC disease caused by a homozygous R132X mutation. The girls presented with neuropsychiatric symptoms at ages 14 and 10 years, respectively.

In a study of 118 patients with cblC disease, Lerner-Ellis et al. (2009) found that individuals with the R132X mutation tended to present with late-onset disease. Transcript and RT-PCR analysis of cblC fibroblasts showed that the R132X mutation resulted in significantly higher levels of transcript compared to cell lines homozygous for the early-onset mutations. The authors postulated that nonsense-mediated decay may not occur with this mutation, or that it may occur to a lesser extent. Alternatively, the mutation may result in a truncated protein with residual function. Lerner-Ellis et al. (2009) identified the R132X mutation in 20% of pathogenic alleles from 118 patients with cblC.