A small deletion in C9orf72 hides a proportion of expansion carriers in FTLD

NEUROBIOLOGY OF AGING

卷:36

Article

Rollinson, Sara¹  Callister, Janis Bennion¹  Young, Kate¹  Ryan, Sarah J.¹  Druyeh, Ronald²  Rohrer, Jonathan D.²  Snowden, Julie³  Richardson, Anna³  Jones, Matt³  Harris, Jenny³  Davidson, Yvonne³  Robinson, Andrew³  Ealing, John⁴  Johnson, Janel O.⁵  Traynor, Bryan⁵  Mead, Simon⁶  Mann, David³  Pickering-Brown, Stuart M.¹ 

[1] Univ Manchester, Inst Brain Behav & Mental Hlth, Fac Human & Med Sci, Manchester M13 9PT, Lancs, England

[2] UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England

[3] Univ Manchester, Fac Human & Med Sci, Salford Royal Hosp, Mental Hlth & Neurodegenerat Res Grp, Salford, Lancs, England

[4] Salford Royal NHS Fdn Trust, Greater Manchester Neurosci Ctr, MND Care Ctr, Salford, Lancs, England

[5] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[6] UCL Inst Neurol, Dept Neurodegenerat Dis, London, England

关键词: Frontotemporal lobar degeneration;    FTLD;    C9orf72;    Repeat expansion;    ALS;   

DOI  :  10.1016/j.neurobiolaging.2014.12.009

来源: Elsevier

【 摘 要 】

Frontotemporal lobar degeneration is a highly familial disease and the most common known genetic cause is the repeat expansion mutation in the gene C9orf72. We have identified 2 brothers with an expansion mutation in C9orf72 using Southern blotting that is undetectable using repeat-primed polymerase chain reaction. Sequencing using high concentrations of DNA denaturants of a bacterial artificial chromosome clone obtained from one of the brothers identified a 10-base pair deletion adjacent to the expansion that presumably confers strong secondary structure that interferes with the genotyping. Using an alternative method, we have identified missed expansion carriers in our cohort, and this number has increased by approximately 25%. This observation has important implications for patients undergoing genetic testing for C9orf72. (C) 2015 The Authors. Published by Elsevier Inc.

【 授权许可】

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