MedicalResearch.com Interview with:
Prof. Dr. Christine Van Broeckhoven PhD DSc
Professor in Molecular Biology and Genetics
, University of Antwerp
Science Director, VIB Center for Molecular Neurology
Research Director, Laboratory for Neurogenetics, Institute Born-Bunge
Senior Group Leader, Neurodegenerative Brain Diseases
University of Antwerp and
Dr. Sara Van Mossevelde, MD
Center for Molecular Neurology, VIB
Institute Born-Bunge, University of Antwerp
Department of Neurology and Memory Clinic
Hospital Network Antwerp Middelheim and Hoge Beuken
Antwerp, Belgium
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Patients with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) and a
C9orf72 repeat expansion present with highly variable onset ages of disease. In the Belgian patient cohort the onset ages ranged from 29 to 82 years of age. This high variability suggested the influence of modifying factors on disease expression. As in other repeat expansion diseases, repeat length is the prime candidate as genetic modifier. In a molecular study (Gijselinck et al., Molecular psychiatry 2016), we were able to provide evidence for an inverse correlation of repeat length with onset age in affected parent – affected children in a C0orf72 families. Also, the degree of methylation of the C9orf72 repeat correlated with repeat size.
In this clinical study of affected parent – affected children pairs we provided additional evidence for the occurrence of disease anticipation in
C9orf72 pedigrees by analyzing age at onset, disease duration and age at death in successive generations. Within 36
C9orf72 pedigrees with available age data of patients in two to four generations, we observed a significant decrease in age at onset across successive generation while no generational effect was seen on disease burden, disease duration or age at death.
(more…)