A novel genomic disorder:: a deletion of the SACS gene leading to Spastic Ataxia of Charlevoix-Saguenay
A novel genomic disorder:: a deletion of the SACS gene leading to Spastic Ataxia of Charlevoix-Saguenay
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DOI：
10.1038/ejhg.2008.58
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发表时间：
2008-09-01
影响因子：
5.2
通讯作者：
Devriendt, Koenraad
中科院分区：
文献类型：
--
作者：
Breckpot, Jeroen;Takiyama, Yoshihisa;Devriendt, Koenraad
我们报告一个比利时的病人与早发性小脑共济失调，进行性痉挛，学习困难和中度感知听力损失。阵列比较基因组杂交（aCGH）检测到染色体13q12.12上的1.54 Mb缺失。这种微缺失从头发生，包括SACS基因。已知SACS中的突变会导致隐性病症，类似于患者的表型，称为常染色体隐性痉挛性共济失调（ARSACS）。对剩余的SACS等位基因进行测序，发现外显子9中存在半合子突变c.10517T>C，导致氨基酸替换（p.F3506S）。这是第一个ARSACS患者携带从头染色体缺失，包括SACS。我们证明了存在同源片段重复的断点包含区域。这表明非等位基因同源重组是产生该缺失的机制，并解释了先前对该区域拷贝数变异的描述。这一发现证实了aCGH对常染色体隐性遗传病基因鉴定的贡献。
We report a Belgian patient with early-onset cerebellar ataxia, progressive spasticity, learning difficulties and moderate perceptive hearing loss. Array-Comparative Genomic Hybridisation (aCGH) detected a 1.54 Mb deletion on chromosome 13q12.12. This microdeletion occurred de novo and encompasses the SACS gene. Mutations in SACS are known to cause a recessive condition, similar to the patient's phenotype, called autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Sequencing of the remaining SACS allele revealed a hemizygous mutation c.10517T>C in exon 9, resulting in an amino-acid substitution (p.F3506S). This is the first patient with ARSACS that carries a de novo chromosomal deletion comprising SACS. We demonstrate the presence of homologous segmental duplications at the breakpoint-containing regions. This suggests non-allelic homologous recombination as the mechanism generating this deletion and explains the previous description of copy number variations of this region. This finding confirms the contribution of aCGH to gene identification in autosomal recessive disorders.