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

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.

journal_name

Neurology

journal_title

Neurology

authors

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

doi

10.1212/WNL.0000000000001883

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

756-62

issue

9

eissn

0028-3878

issn

1526-632X

pii

WNL.0000000000001883

journal_volume

85

pub_type

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