Dataset Information

Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy.

ABSTRACT: 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 arv1? 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.

SUBMITTER: Palmer EE

PROVIDER: S-EPMC5181598 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy.

Palmer Elizabeth E EE Jarrett Kelsey E KE Sachdev Rani K RK Al Zahrani Fatema F Hashem Mais Omar MO Ibrahim Niema N Sampaio Hugo H Kandula Tejaswi T Macintosh Rebecca R Gupta Rajat R Conlon Donna M DM Billheimer Jeffrey T JT Rader Daniel J DJ Funato Kouichi K Walkey Christopher J CJ Lee Chang Seok CS Loo Christine C Brammah Susan S Elakis George G Zhu Ying Y Buckley Michael M Kirk Edwin P EP Bye Ann A Alkuraya Fowzan S FS Roscioli Tony T Lagor William R WR

Human molecular genetics 20160606 14

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 ...[more]

PMID: 27270415

Dataset Information

Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy.

Publications

Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy.

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