Whole-genome sequencing identifies a c.1282C > T missense variant in Taurine Transporter (TauT) associated with taurine-mediated dilated cardiomyopathy in a family of domestic shorthair cats

10/09/2026

AI Summary

Whole-genome association study identified a c.1282C>T; p.Arg428Trp variant in SLC6A6 (TauT) segregating with incomplete dominance in affected cats.
Mutant TauT showed markedly reduced cellular taurine uptake and decreased plasma membrane expression in HEK293-derived cell functional assays.
This variant explains taurine deficiency associated dilated cardiomyopathy in the family, the first genetic cause of taurine deficiency reported in a domestic species.

AI Summary

In most mammals, taurine is synthesized via methionine transsulfuration; albeit, in cats, taurine biosynthesis is blunted due to low enzymatic activity of their encoded cysteine sulfonic acid decarboxylase and, therefore, is an essential amino acid in the species.

Severe dilated cardiomyopathy and taurine deficiency were identified, despite eating a commercial, nutritionally balanced, diet with adequate taurine concentrations.

A whole-genome association study (WGAS), under the assumptions of an incomplete dominance mode of inheritance (MOI), was performed on this case and two related cats with mild taurine and echocardiographic abnormalities (i.e., queen and littermate) compared to 18 previously whole-genome sequenced echocardiographically-normal geriatric controls (>10 years-of-age; n = 21).

Basic summary

J Mol Cell Cardiol. 2026 Sep 9:S0022-2828(26)00147-1. doi: 10.1016/j.yjmcc.2026.09.001. Online ahead of print.

ABSTRACT

Taurine is a cytoprotectant amino acid critical for a variety of cellular functions, including cell volume and intracellular calcium regulation, bile salt formation, free radical protection, and mitochondrial biogenesis. In most mammals, taurine is synthesized via methionine transsulfuration; albeit, in cats, taurine biosynthesis is blunted due to low enzymatic activity of their encoded cysteine sulfonic acid decarboxylase and, therefore, is an essential amino acid in the species. Taurine deficiency in cats results in retinopathy, coagulopathy, growth retardation, impaired immunological function, and most notably dilated cardiomyopathy (DCM). A three-year-old domestic shorthair cat was evaluated for vomiting, anorexia, and lethargy. Severe dilated cardiomyopathy and taurine deficiency were identified, despite eating a commercial, nutritionally balanced, diet with adequate taurine concentrations. A whole-genome association study (WGAS), under the assumptions of an incomplete dominance mode of inheritance (MOI), was performed on this case and two related cats with mild taurine and echocardiographic abnormalities (i.e., queen and littermate) compared to 18 previously whole-genome sequenced echocardiographically-normal geriatric controls (>10 years-of-age; n = 21). A ‘MODERATE’ c.1282C > T; p.Arg428Trp variant harbored in Solute Carrier Family 6 Member 6/Taurine Transporter (SLC6A6/TauT) was identified. The variant segregated to the postulated MOI and was not observed in any of the control or in an expanded population of cats (n = 422). Functional analyses involving wildtype and mutant SLC6A6 overexpression in HEK293-derived cells revealed marked reduction in cellular taurine uptake and decreased plasma membrane expression in those harboring the c.1282C > T variant. This represents the first-ever reported genetic variant explaining taurine deficiency in any domestic animal species.

PMID:42716424 | DOI:10.1016/j.yjmcc.2026.09.001

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