Whole-Exome Sequencing Reveals a Rare Missense Variant in SLC16A9 in a Pedigree with Early-Onset Gout

الملخص EN

Gout is a common inflammatory arthritis triggered by monosodium urate deposition after longstanding hyperuricemia.

In the general community, the disease is largely polygenic in genetic architecture, with many polymorphisms having been identified in gout or urate-associated traits.

In a small proportion of cases, rare high penetrant mutations associated with monogenic segregation of the disease in families have been demonstrated to be disease causative.

In this study, we recruited a two-generation pedigree with early-onset gout.

To elucidate the genetic predisposition, whole-exome sequencing (WES) was performed.

After comprehensive variant analyses and cosegregation testing, we identified a missense variant (c.277C>A, p.L93M) in SLC16A9, an extremely rare variant in genetic databases.

Moreover, in silico assessments showed strong pathogenicity.

This variant cosegregated with the disease phenotype perfectly in the family and is located in a highly conserved functional domain.

A few studies supported our results of the association between SLC16A9 and gout and serum urate levels.

In conclusion, we provide the first evidence for the association of rare missense in SLC16A9 with early-onset gout.

These findings not only expand our current understanding of gout but also may have further implications for the treatment and prevention of gout.