Concetta Scimone, Simona Alibrandi, Luigi Donato, Teresa Esposito, Antonina Sidoti, Rosalia D’Angelo
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.