A novel genomic disorder:: a deletion of the SACS gene leading to Spastic Ataxia of Charlevoix-Saguenay

被引:39
作者
Breckpot, Jeroen [1 ]
Takiyama, Yoshihisa [2 ]
Thienpont, Bernard [1 ]
Van Vooren, Steven [3 ]
Vermeesch, Joris Robert [1 ]
Ortibus, Els [4 ]
Devriendt, Koenraad [1 ]
机构
[1] Univ Hosp Leuven, Ctr Human Genet, B-3000 Louvain, Belgium
[2] Jichi Med Univ, Dept Internal Med, Div Neurol, Tochigi, Japan
[3] Catholic Univ Louvain, Dept Elect Engn ESAT, B-3000 Louvain, Belgium
[4] Catholic Univ Louvain, Dept Paediat Neurol, B-3000 Louvain, Belgium
关键词
ARSACS; chromosomal deletion; array CGH;
D O I
10.1038/ejhg.2008.58
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1050 / 1054
页数:5
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