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

Heather C. Mefford*, Matthew Zemel, Eileen Geraghty, Joseph Cook, Peter T. Clayton, Karl Paul, Barbara Plecko, Philippa B. Mills, Douglas R. Nordli, Sidney M. Gospe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)756-762
Number of pages7
JournalNeurology
Volume85
Issue number9
DOIs
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Clinical Neurology

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