Sequencing analysis of the spinal bulbar muscular atrophy CAG expansion reveals absence of repeat interruptions

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• 作者：Pietro Fratta ; Toby Collins ; Sally Pemble ; Suran Nethisinghe ; Anny Devoy ; Paola Giunti ; Mary G. Sweeney ; Michael G. Hanna ; Elizabeth M.C. Fisher
• 关键词：Kennedy's disease ; Spinal bulbar muscular atrophy ; CAG ; Trinucleotide ; Interruptions
• 刊名：Neurobiology of Aging
• 出版年：February, 2014
• 年：2014
• 卷：35
• 期：2
• 页码：443.e1-443.e3
• 全文大小：164 K

文摘

Trinucleotide repeat disorders are a heterogeneous group of diseases caused by the expansion, beyond a pathogenic threshold, of unstable DNA tracts in different genes. Sequence interruptions in the repeats have been described in the majority of these disorders and may influence disease phenotype and heritability. Spinal bulbar muscular atrophy (SBMA) is a motor neuron disease caused by a CAG trinucleotide expansion in the androgen receptor (m>ARm>) gene. Diagnostic testing and previous research have relied on fragment analysis polymerase chain reaction to determine the m>ARm> CAG repeat size, and have therefore not been able to assess the presence of interruptions. We here report a sequencing study of the m>ARm> CAG repeat in a cohort of SBMA patients and control subjects in the United Kingdom. We found no repeat interruptions to be present, and we describe differences between sequencing and traditional sizing methods.