Intragenic deletions of ALDH7A1 in pyridoxine-dependent epilepsy caused by Alu-Alu recombination.

Published

Journal Article

OBJECTIVE: To investigate the role of intragenic deletions of ALDH7A1 in patients with clinical and biochemical evidence of pyridoxine-dependent epilepsy but only a single identifiable mutation in ALDH7A1. METHODS: We designed a custom oligonucleotide array with high-density probe coverage across the ALDH7A1 gene. We performed array comparative genomic hybridization in 6 patients with clinical and biochemical evidence of pyridoxine-dependent epilepsy but only a single detectable mutation in ALDH7A1 by sequence analysis. RESULTS: We found partial deletions of ALDH7A1 in 5 of 6 patients. Breakpoint analysis reveals that the deletions are likely a result of Alu-Alu recombination in all cases. The density of Alu elements within introns of ALDH7A1 suggests susceptibility to recurrent rearrangement. CONCLUSION: Patients with clinical pyridoxine-dependent epilepsy and a single identifiable mutation in ALDH7A1 warrant further investigation for copy number changes involving the ALHD7A1 gene.

Full Text

Duke Authors

Cited Authors

  • Mefford, HC; Zemel, M; Geraghty, E; Cook, J; Clayton, PT; Paul, K; Plecko, B; Mills, PB; Nordli, DR; Gospe, SM

Published Date

  • September 1, 2015

Published In

Volume / Issue

  • 85 / 9

Start / End Page

  • 756 - 762

PubMed ID

  • 26224730

Pubmed Central ID

  • 26224730

Electronic International Standard Serial Number (EISSN)

  • 1526-632X

Digital Object Identifier (DOI)

  • 10.1212/WNL.0000000000001883

Language

  • eng

Conference Location

  • United States