期刊
GENETICS IN MEDICINE
卷 16, 期 5, 页码 386-394出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gim.2013.155
关键词
autosomal recessive; Charcot-Marie-Tooth disease; CMT4D; CNV; NDRG1
资金
- US National Institute of Neurological Disorders and Stroke [R01NS058529]
- US National Human Genome Research Institute (NHGRI) [U54HG006542]
- NHGRI [U54-HG003273]
- Bogazici University Research Fund [09B101]
- Neuroimmunology Association (NIMDER)
Purpose: Copy-number variations as a mutational mechanism contribute significantly to human disease. Approximately one-half of the patients with Charcot-Marie-Tooth (CMT) disease have a 1.4Mb duplication copy-number variation as the cause of their neuropathy. However, non-CMTIA neuropathy patients rarely have causative copy-number variations, and to date, autosomal-recessive CMT disease has not been associated with copy-number Variation as a mutational mechanism. Methods: We performed Agilent 8 x 60K array comparative genomic hybridization on DNA from 12 recessive Turkish families with CMT disease. Additional molecular studies were conducted to detect breakpoint junctions and to evaluate gene expression levels in a family in which we detected an intragenic duplication copy-number variation. Results: We detected an similar to 6.25 kb homozygous intragenic duplication in NDRG1, a gene known to be causative for recessive HMSNL/CMT4D, in three individuals from a Turkish family with CMT neuropathy. Further studies showed that this intragenic copy-number variation resulted in a homozygous duplication of exons 6-8 that caused decreased mRNA expression. of NDRG1. Conclusion: Exon-focused high-resolution array comparative ! genomic hybridization enables the detection of copy-number variation carrier states in recessive genes, particularly small copy-number variations encompassing or disrupting single genes. In families for whom. a molecular diagnosis has not been elucidated by conventional clinical assays, an assessment for copy-number variations in known CMT genes might be considered.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据