Low penetrance in facioscapulohumeral muscular dystrophy type 1 with large pathological D4Z4 alleles: a cross-sectional multicenter study
- Creators
- Salort Campana, Emmanuelle
- Nguyen, Karine
- Bernard, Rafaelle
- Jouve, Elisabeth
- Solé, Guilhem
- Nadaj-Pakleza, Aleksandra
- Niederhauser, Julien
- Charles, Estelle
- Ollagnon, Elisabeth
- Bouhour, Françoise
- Sacconi, Sabrina
- Echaniz-Laguna, Andoni
- Desnuelle, Claude
- Tranchant, Christine
- Vial, Christophe
- Magdinier, Frédérique
- Bartoli, Marc
- Arné-Bes, Marie-Christine
- Ferrer, Xavier
- Kuntzer, Thierry
- Lévy, Nicolas
- Pouget, Jean
- Attarian, Shahram
- Others:
- Génétique Médicale et Génomique Fonctionnelle (GMGF) ; Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Centre de référence des maladies neuromusculaires et de la SLA ; Hôpital de la Timone [CHU - APHM] (TIMONE)
- Département de génétique médicale [Hôpital de la Timone - APHM] ; Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Hôpital de la Timone [CHU - APHM] (TIMONE)
- Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest ; CHU Bordeaux [Bordeaux]
- Centre de reference des maladies neuromusculaires Nantes-Angers, CHU d'Angers et Nantes ; Centre Hospitalier Universitaire d'Angers (CHU Angers) ; PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)
- Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)
- Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET) ; Assistance Publique - Hôpitaux de Marseille (APHM)
- Hôpital de la Croix-Rousse [CHU - HCL] ; Hospices Civils de Lyon (HCL)
- Hôpital neurologique ; Hospices Civils de Lyon (HCL)
- Institut de Biologie Valrose (IBV) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Hôpital de Hautepierre [Strasbourg]
- Pôle Tête-Cou-CETD ; Les Hôpitaux Universitaires de Strasbourg (HUS)
- Neurologie et Explorations Fonctionnelles du Système Nerveux [Toulouse] ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Description
Background: Facioscapulohumeral muscular dystrophy type 1(FSHD1) is an autosomal dominant disorder associated with the contraction of D4Z4 less than 11 repeat units (RUs) on chromosome 4q35. Penetrance in the range of the largest alleles is poorly known. Our objective was to study the penetrance of FSHD1 in patients carrying alleles ranging between 6 to 10 RUs and to evaluate the influence of sex, age, and several environmental factors on clinical expression of the disease. Methods: A cross-sectional multicenter study was conducted in six French and one Swiss neuromuscular centers. 65 FSHD1 affected patients carrying a 4qA allele of 6-10 RUs were identified as index cases (IC) and their 119 at-risk relatives were included. The age of onset was recorded for IC only. Medical history, neurological examination and manual muscle testing were performed for each subject. Genetic testing determined the allele size (number of RUs) and the 4qA/4qB allelic variant. The clinical status of relatives was established blindly to their genetic testing results. The main outcome was the penetrance defined as the ratio between the number of clinically affected carriers and the total number of carriers. Results: Among the relatives, 59 carried the D4Z4 contraction. At the clinical level, 34 relatives carriers were clinically affected and 25 unaffected. Therefore, the calculated penetrance was 57% in the range of 6-10 RUs. Penetrance was estimated at 62% in the range of 6-8 RUs, and at 47% in the range of 9-10 RUs. Moreover, penetrance was lower in women than men. There was no effect of drugs, anesthesia, surgery or traumatisms on the penetrance. Conclusions: Penetrance of FSHD1 is low for largest alleles in the range of 9-10 RUs, and lower in women than men. This is of crucial importance for genetic counseling and clinical management of patients and families.
Abstract
International audience
Additional details
- URL
- https://hal.science/hal-01610016
- URN
- urn:oai:HAL:hal-01610016v1
- Origin repository
- UNICA