Mefford Heather C, Zemel Matthew, Geraghty Eileen, Cook Joseph, Clayton Peter T, Paul Karl, Plecko Barbara, Mills Philippa B, Nordli Douglas R, Gospe Sidney M
From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
Neurology. 2015 Sep 1;85(9):756-62. doi: 10.1212/WNL.0000000000001883. Epub 2015 Jul 29.
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.
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.
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.
Patients with clinical pyridoxine-dependent epilepsy and a single identifiable mutation in ALDH7A1 warrant further investigation for copy number changes involving the ALHD7A1 gene.
研究醛脱氢酶7A1（ALDH7A1）基因内缺失在有维生素B6依赖型癫痫临床和生化证据但ALDH7A1仅有一个可识别突变的患者中的作用。
我们设计了一种定制的寡核苷酸阵列，其对ALDH7A1基因具有高密度探针覆盖。我们对6例有维生素B6依赖型癫痫临床和生化证据但通过序列分析在ALDH7A1中仅有一个可检测突变的患者进行了阵列比较基因组杂交。
我们在6例患者中的5例发现了ALDH7A1的部分缺失。断点分析显示，在所有病例中，缺失可能是Alu - Alu重组的结果。ALDH7A1内含子内Alu元件的密度表明其易发生反复重排。
有临床维生素B6依赖型癫痫且ALDH7A1有一个可识别突变的患者，有必要进一步研究涉及ALHD7A1基因的拷贝数变化。
