| First Author | Palmer EE | Year | 2016 |
| Journal | Hum Mol Genet | Volume | 25 |
| Issue | 14 | Pages | 3042-3054 |
| PubMed ID | 27270415 | Mgi Jnum | J:237145 |
| Mgi Id | MGI:5811197 | Doi | 10.1093/hmg/ddw157 |
| Citation | Palmer EE, et al. (2016) Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy. Hum Mol Genet 25(14):3042-3054 |
| abstractText | We report an individual who presented with severe neurodevelopmental delay and an intractable infantile-onset seizure disorder. Exome sequencing identified a homozygous single nucleotide change that abolishes a splice donor site in the ARV1 gene (c.294 + 1G > A homozygous). This variant completely prevented splicing in minigene assays, and resulted in exon skipping and an in-frame deletion of 40 amino acids in primary human fibroblasts (NP_073623.1: p.(Lys59_Asn98del). The p.(Lys59_Asn98del) and previously reported p.(Gly189Arg) ARV1 variants were evaluated for protein expression and function. The p.(Gly189Arg) variant partially rescued the temperature-dependent growth defect in arv1Delta yeast, while p.(Lys59-Asn98del) completely failed to rescue at restrictive temperature. In contrast to wild type human ARV1, neither variant expressed detectable levels of protein in mammalian cells. Mice with a neuronal deletion of Arv1 recapitulated the human phenotype, exhibiting seizures and a severe survival defect in adulthood. Our data support ARV1 deficiency as a cause of autosomal recessive epileptic encephalopathy. |
