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A novel mutation in RNF216 gene in an Indian case with Gordon Holmes syndrome
  1. Arjun Bal Kallupurakkal,
  2. Rajesh Verma and
  3. Rajarshi Chakraborty
  1. Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
  1. Correspondence to Professor Rajesh Verma; drrajeshverma32{at}


Early-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 as described by Sir Gordon Holmes in 1908 consists of ataxia with hypogonadism. It is due to mutation in RNF216 and OTUD4 genes which encode for enzymes in the ubiquitin-proteasome system. In this case report, we describe a 30-year-old male presenting with insidious-onset progressive ataxia with hypogonadotropic hypogonadism, cataract, pan-cerebellar atrophy with bilateral cerebral white matter hyperintensities and a positive homozygous mutation for RNF216 making the diagnosis of Gordon Holmes syndrome. The presence of hypogonadism in a patient with ataxia should alert the clinician to look for such a diagnosis.

  • Neuro genetics
  • Neuroimaging

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  • Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: RV, ABK, RC. The following authors gave final approval of the manuscript: RV, ABK, RC.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.