open access
TRIO gene segregation in a family with cerebellar ataxia
open access
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.
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.
Keywords
Spinocerebellar ataxia, Gait disorder/ataxia, Cerebellum, Mental retardation
About this articleTitle
TRIO gene segregation in a family with cerebellar ataxia
Journal
Neurologia i Neurochirurgia Polska
Issue
Pages
743-749
Pubmed
Bibliographic record
Neurol Neurochir Pol 2018;52(6):743-749.
Keywords
Spinocerebellar ataxia
Gait disorder/ataxia
Cerebellum
Mental retardation
Authors
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