Title :

Deciphering the complexity of the 4q and 10q subtelomeres by molecular combing in healthy individuals and patients with facioscapulohumeral dystrophy.

Author(s) :

Nguyen, Karine [Auteur]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
CHU Marseille
Broucqsault, Natacha [Auteur]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Chaix, Charlene [Auteur]
Département de génétique médicale [Hôpital de la Timone - APHM]
Roche, Stéphane [Auteur]
Hôpital Pierre Zobda-Quitman [CHU de la Martinique]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Robin, Jerome D [Auteur]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Vovan, Catherine [Auteur]
Département de génétique médicale [Hôpital de la Timone - APHM]
Gerard, Laurene [Auteur]
Assistance Publique - Hôpitaux de Marseille [APHM]
Mégarbané, Andre [Auteur]
Institut Jérôme Lejeune
Urtizberea, Jon-Andoni [Auteur]
Hôpital Marin d'Hendaye
Assistance publique - Hôpitaux de Paris (AP-HP) [AP-HP]
Bellance, Remi [Auteur]
Hôpital Pierre Zobda-Quitman [CHU de la Martinique]

Barnérias, Christine [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Filière Neuromusculaire [FILNEMUS]
David, Albert [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Eymard, Bruno [Auteur]
Assistance publique - Hôpitaux de Paris (AP-HP) [AP-HP]
Fradin, Melanie [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Service de génétique clinique [Rennes]
Manel, Veronique [Auteur]
Hôpital Femme Mère Enfant [CHU - HCL] [HFME]
Hospices Civils de Lyon [HCL]
Sacconi, Sabrina [Auteur]
Université Côte d'Azur [UniCA]
Tiffreau, Vincent [Auteur]
Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369
Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS]
Zagnoli, Fabien [Auteur]
Centre Hospitalier Régional Universitaire de Brest [CHRU Brest]
Cuisset, Jean-Marie [Auteur]
Service de Neuro-pédiatrie[Lille]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Salort-Campana, Emmanuelle [Auteur]
Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Attarian, Shahram [Auteur]
Hôpital de la Timone [CHU - APHM] [TIMONE]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Bernard, Rafaelle [Auteur]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Département de génétique médicale [Hôpital de la Timone - APHM]
Lévy, Nicolas [Auteur]
Hôpital de la Timone [CHU - APHM] [TIMONE]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]
Magdinier, Frederique [Auteur]
Marseille medical genetics - Centre de génétique médicale de Marseille [MMG]

Journal title :

Journal of Medical Genetics

Abbreviated title :

J. Med. Genet.

Publication date :

2019-04-22

ISSN :

1468-6244

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

BACKGROUND: Subtelomeres are variable regions between telomeres and chromosomal-specific regions. One of the most studied pathologies linked to subtelomeric imbalance is facioscapulohumeral dystrophy (FSHD). In most cases, ...
Show more >BACKGROUND: Subtelomeres are variable regions between telomeres and chromosomal-specific regions. One of the most studied pathologies linked to subtelomeric imbalance is facioscapulohumeral dystrophy (FSHD). In most cases, this disease involves shortening of an array of D4Z4 macrosatellite elements at the 4q35 locus. The disease also segregates with a specific A-type haplotype containing a degenerated polyadenylation signal distal to the last repeat followed by a repetitive array of β-satellite elements. This classification applies to most patients with FSHD. A subset of patients called FSHD2 escapes this definition and carries a mutation in the gene. We also recently described patients carrying a complex rearrangement consisting of a -duplication of the distal 4q35 locus identified by molecular combing. METHODS: Using this high-resolution technology, we further investigated the organisation of the 4q35 region linked to the disease and the 10q26 locus presenting with 98% of homology in controls and patients. RESULTS: Our analyses reveal a broad variability in size of the different elements composing these loci highlighting the complexity of these subtelomeres and the difficulty for genomic assembly. Out of the 1029 DNA samples analysed in our centre in the last 7 years, we also identified 54 cases clinically diagnosed with FSHD carrying complex genotypes. This includes mosaic patients, patients with deletions of the proximal 4q region and 23 cases with an atypical chromosome 10 pattern, infrequently found in the control population and never reported before. CONCLUSIONS: Overall, this work underlines the complexity of these loci challenging the diagnosis and genetic counselling for this disease.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Univ. Littoral Côte d’Opale
Univ. Artois
Université de Lille

Collections :

• Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369

Research team(s) :

Activité Physique, Muscle, Santé (APMS)

Submission date :

2019-09-24T10:02:05Z
2024-02-23T14:49:40Z