VARIANTS OF THE MOLECULAR CHAPERONE HSPA8 AND HSPA1A GENES IN TRIMETHYLAMINURIA: A PILOT STUDY

There is discrepancy in the phenotypic manifestations of trimethylaminuria (TMAU) between

patients suggesting a certain diversity of etiological-pathogenic factors. Primary TMAU is linked to

mutations in the FMO3 gene but a proportion of patients do not carry mutations in it or carry single

nucleotide polymorphisms (SNPs) that do not have an impact on the gene’s product, the enzyme

FMO3. It remains to be established what other factors are pathogenic in TMAU underpinning the

various phenotypes. We hypothesized that defective chaperones could contribute to the

pathogenesis by, for example, failing to assist FMO3 in its folding and refolding cycles. In the

initial screening reported here we investigated two chaperone genes, HSPA8 and HSPA1A in

twelve TMAU patients and found that variants in the former were highly represented in comparison

with controls. Further studies, including more patients are underway to firmly establish the

prevalence of the variants and to begin elucidating molecular mechanisms