| Title |
Cerebellar ataxia and peripheral neuropathy in a family with PNPLA8-associated disease / |
| Authors |
Burnytė, Birutė ; Vilimienė, Ramunė ; Grigalionienė, Kristina ; Adomaitienė, Irina ; Utkus, Algirdas |
| DOI |
10.1212/NXG.0000000000200068 |
| Full Text |
|
| Is Part of |
Neurology ; Genetics.. Philadelphia : Lippincot Williams & Wilkins. 2023, vol. 9, no. 3, art. no. e200068, p. [1-5].. ISSN 2376-7839 |
| Keywords [eng] |
cerebellar ataxia ; peripheral neuropathy ; PNPLA8-associated disease |
| Abstract [eng] |
Objectives To describe clinical and genetic findings in 2 siblings with slowly progressive ataxia. Methods We studied 2 adult siblings through detailed physical and instrumental examinations. Whole- exome sequencing was used to identify an underlying genetic cause. Results Both siblings presented with adolescence-onset ataxia, progressive sensorimotor poly- neuropathy, 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)) in PNPLA8. The novel variant c.2269del results in frameshift with a premature stop codon p.(Thr757GlnfsTer10) and loss of normal enzyme function. Discussion Our findings support the theory that biallelic loss-of-function PNPLA8 variants 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 pro- gression of ataxia throughout adulthood. |
| Published |
Philadelphia : Lippincot Williams & Wilkins |
| Type |
Journal article |
| Language |
English |
| Publication date |
2023 |
| CC license |
|
