Relationship between C9orf72 repeat size and clinical phenotype.
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.
Center 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.
Sara
S
Van Mossevelde
Center for Molecular Neurology, VIB, Universiteitsplein 1, 2610 Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
Julie
J
van der Zee
Center for Molecular Neurology, VIB, Universiteitsplein 1, 2610 Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
Marc
M
Cruts
Center for Molecular Neurology, VIB, Universiteitsplein 1, 2610 Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address: christine.vanbroeckhoven@molgen.vib-ua.be.
Christine
C
Van Broeckhoven
D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000073885:C9orf72 Protein / Q000235:genetics*; D042622:DNA Repeat Expansion / Q000235:genetics*; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009030:Mosaicism; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human