Identification of a large homozygous RNF216 deletion in a Chinese patient with gordon holmes syndrome.

backgroundEarly-onset cerebellar ataxia has a broad range of challenging differential diagnoses. Identification of hypogonadism can assist in narrowing down differential diagnosis in the presentation of progressive ataxia. Gordon Holmes syndrome is a rare autosomal recessive disease characterized by hypogonadotropic hypogonadism, cerebellar ataxia, and progressive cognitive decline. CASE PRESENTATION: We identify a novel homozygous deletion mutations of RNF216 causing GHS. The proband presented with dysarthria and gait ataxia. Cerebellar atrophy and white matter lesions were found in the cerebral hemispheres and brainstem. Low gonadotropin serum levels were also observed. Whole-exome sequencing and Chromosome analysis by medium coverage whole genome sequencing (CMA-seq) revealed a novel homozygous deletion mutations from exon1 to exon7 in RNF216 (chr7:5762980-5831600). Nested polymerase chain reaction (PCR) and agarose gel electrophoresis were performed to identify the deletion fragments. Sanger sequencing was also performed to find out the accurate breakpoint.

conclusionWe report the first female Chinese patient of GHS. The core features of GHS are well defned. By using the genetic sequencing and chromosome analysis, we identified a novel 68Kb deletion at RNF216 gene. Thus, CMA-seq had promising potentiality in genetic screening of GHS, especially for the novel deletions mutations in RNF216 gene.