Gordon Holmes syndrome caused by two novel mutations in the PNPLA6 gene

Gordon Holmes syndrome (GHS) is an autosomal recessive disease characterized by cerebellar ataxia and hypogonadotropic hypogonadism. Among the genes associated with this syndrome, mutations in PNPLA6 have been detected and correlated with the phenotype of GHS. We report a case of a patient affected with GHS, confirmed by physical, neurological, laboratory and genetic analyses. Two compound heterozygous missense mutations on the PNPLA6 gene described as probably damaging/damaging in multiple in silico predictive tools have been detected with massive multigene sequencing. Interestingly, brain MRI uncovered abnormalities in the periventricular white matter, which so far have not been associated with GHS caused by PNPLA6 mutations.