TRIO gene segregation in a family with cerebellar ataxia

Rana Hanna Al Shaikh, Thomas Caulfield, Audrey J. Strongosky, Mavis Matthew, Karen R. Jansen-West, Mercedes Prudencio, John D. Fryer, Leonard Petrucelli, Ryan J. Uitti, Zbigniew K. Wszolek

Research output: Contribution to journalArticle

Abstract

Aim of the study: To report a family with a novel TRIO gene mutation associated with phenotype of cerebellar ataxia. Materials and methods: Seven family members of Caribbean descent were recruited through our ataxia research protocol; of the family members, the mother and all 3 children were found to be affected with severe young-onset and rapidly progressive truncal and appendicular ataxia leading to early disability. Array comparative genomic hybridization, mitochondrial DNA analysis, and whole-exome sequencing were performed on 3 of the family members (mother and 2 daughters). Results: While the maternal grandmother, great uncle and great aunt were unaffected, the mother and 3 children displayed cognitive dysfunction, severe ataxia, spasticity, and speech disturbances. Age of onset ranged between 3 and 17 years, with average current disease duration of 21 years. Whole-exome sequencing showed a variant p.A1214V in exon 22 of the TRIO gene in 3 of the family members. Array comparative genomic hybridization and mitochondrial DNA analysis were normal. The same variant was later discovered in all but one family member. Conclusions and clinical implications: The TRIO p.A1214V variant is associated with cerebellar ataxia in the studied family; it was present in all affected and unaffected family members. Phenotype is severe and broad. Anticipation seems to be present (based on 2 affected generations). It is warranted to screen additional familial early-onset and rapidly progressive ataxia cases for this genotype. TRIO gene mutations may well represent a novel spinocerebellar ataxia subtype.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
JournalNeurologia i neurochirurgia polska
Volume52
Issue number6
DOIs
StatePublished - Nov 1 2018

Keywords

  • Cerebellum
  • Gait disorder/ataxia
  • Mental retardation
  • Spinocerebellar ataxia

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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