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Relationship between C9orf72 repeat size and clinical phenotype
Sara Van Mossevelde1, Julie van der Zee2, Marc Cruts2
1Center for Molecular Neurology, VIB, Universiteitsplein 1, 2610 Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp Hoge Beuken, Commandant Weynsstraat 165, 2660 Hoboken, Belgium; Department of Neurology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium.
Abstract:
Patient carriers of a C9orf72 repeat expansion exhibit remarkable heterogeneous clinical and pathological characteristics suggesting the presence of modifying factors. In accordance with other repeat expansion diseases, repeat length is the prime candidate as a genetic modifier. Observations of earlier onset ages in younger generations of large families suggested a mechanism of disease anticipation. Yet, studies of repeat size and onset age have led to conflicting results. Also, the correlation between repeat size and diagnosis is poorly understood. We review what has been published regarding C9orf72 repeat size as modifier for phenotypic characteristics. Conclusive evidence is lacking, partly due to the difficulties in accurately defining the exact repeat size and the presence of repeat variability due to somatic mosaicism.
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