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Cerebellar Ataxia and Peripheral Neuropathy in a Family WithPNPLA8-Associated Disease
- Source :
- Neurology ; genetics, Philadelphia : Lippincot Williams & Wilkins, 2023, vol. 9, no. 3, art. no. e200068, p. [1-5]
- Publication Year :
- 2023
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2023.
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Abstract
- ObjectivesTo describe clinical and genetic findings in 2 siblings with slowly progressive ataxia.MethodsWe studied 2 adult siblings through detailed physical and instrumental examinations. Whole-exome sequencing was used to identify an underlying genetic cause.ResultsBoth siblings presented with adolescence-onset ataxia, progressive sensorimotor polyneuropathy, and preserved cognition over time. The onset of symptoms was between 10 and 14 years of age. A brain MRI demonstrated mild cerebellar atrophy in the older brother at age 45 years. Exome sequencing revealed compound heterozygous loss-of-function variants c.2269del (p.(Thr757GlnfsTer10)) and c.2275_2276del (p.(Leu759AlafsTer4)) inPNPLA8. The novel variant c.2269del results in frameshift with a premature stop codon p.(Thr757GlnfsTer10) and loss of normal enzyme function.DiscussionOur findings support the theory that biallelic loss-of-functionPNPLA8variants are involved in neurodegenerative mitochondrial disease. Compared with patients previously described, these patients' phenotype may be interpreted as a milder phenotype associated with a slight progression of ataxia throughout adulthood.
Details
- ISSN :
- 23767839
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Neurology Genetics
- Accession number :
- edsair.doi.dedup.....db5376f77a87e5848d7543de20767977
- Full Text :
- https://doi.org/10.1212/nxg.0000000000200068