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June 29, 2016

Gene mutations and hypogonadotropic hypogonadism

Photo by Action Press / Rex Features

The FGF17 and IL17RD genes are the two top candidates in the entire proteome that may contribute to the genetics of congenital hypogonadotropic hypogonadism (CHH), new research has found.

According to a Swiss-US paper in the American Journal of Human Genetics, researchers set out to determine whether mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations.

The team set out to investigate whether CHH individuals harboured mutations in members of the so-called FGF8 synexpression group, and sought to validate the ability of a bioinformatics algorithm on the basis of interactome-based affiliation scoring (IBAS) to identify high-quality candidate genes.

Seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. The researchers found that except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n=3 individuals), IL17RD (n=8), DUSP6 (n=5), SPRY4 (n=14), and FLRT3 (n=3).

Independently, IBAS predicted FGF17 and IL17RD as the two top candidates on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH.

“Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS [Kallmann syndrome] individuals and were strongly linked to hearing loss (6/8 individuals),” said the authors.

Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008.