Nickerson Sarah L, Marquis-Nicholson Renate, Claxton Karen, Ashton Fern, Leong Ivone U S, Prosser Debra O, Love Jennifer M, George Alice M, Taylor Graham, Wilson Callum, Gardner R J McKinlay, Love Donald R
Diagnostic Genetics, LabPLUS, Auckland City Hospital, P.O. Box 110031, Auckland 1148, New Zealand.
Centre for Translational Pathology, University of Melbourne, Corner Grattan Street and Royal Parade, Parkville, Victoria 3010, Australia.
Microarrays (Basel). 2015 Oct 23;4(4):490-502. doi: 10.3390/microarrays4040490.
Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.
常染色体隐性遗传性小脑共济失调涵盖了一大类异质性神经退行性疾病。我们采用单核苷酸多态性（SNP）分析和全外显子组测序来研究一个患有共济失调的近亲毛利人家系。我们在SACS基因第10外显子中发现了一个新的突变：c.7962T>G p.(Tyr2654*)，从而确诊为夏尔沃-萨格奈常染色体隐性遗传性痉挛性共济失调（ARSACS）。我们的研究结果扩展了这种罕见疾病的遗传和表型谱，并突出了高密度SNP分析和全外显子组测序作为强大且经济高效的工具在诊断遗传性共济失调等遗传异质性疾病中的价值。
