Ataxia and hypogonadotropic hypogonadism with intrafamilial variability caused by RNF216 mutation

Abstract

Gordon Holmes syndrome (GHS) is a distinct phenotype of autosomal recessive cerebellar ataxia, characterized by ataxia, dementia, reproductive defects and hypogonadism; it has been recently found to be associated with <em>RNF216</em> mutation. We performed whole-exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome. We identified a novel splicing variant in <em>RNF216</em> that is likely to abolish the canonical splice site at the junction of exon/intron 13 (NM_207111.3:c.2061G&gt;A). We herein report two patients with GHS caused by a novel <em>RNF216</em> mutation as the first follow up report on <em>RNF216</em>-related GHS, and <em>show</em> interfamilial variability of phenotype supporting the previously reported RNF216-related cases.