Title :

Bethlem myopathy: long-term follow-up identifies COL6 mutations predicting severe clinical evolution

Author(s) :

Deconinck, Nicolas [Auteur]
Richard, Pascale [Auteur]
Allamand, V. [Auteur]
Behin, A. [Auteur]
Laforêt, Pascal [Auteur]
Ferreiro, Ana [Auteur]
De Becdelievre, A. [Auteur]
Ledeuil, C. [Auteur]
Gartioux, C. [Auteur]
Nelson, Isabelle [Auteur]
Carlier, R. Y. [Auteur]
Carlier, P. [Auteur]
Wahbi, Karim [Auteur]
Romero, Norma [Auteur]
Zabot, M. T. [Auteur]
Bouhour, Françoise [Auteur]
Tiffreau, Vincent [Auteur]
Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369
Lacour, Arnaud [Auteur]
Eymard, Bruno [Auteur]
Stojkovic, Tanya [Auteur]

Journal title :

Journal of neurology, neurosurgery, and psychiatry

Abbreviated title :

J. Neurol. Neurosurg. Psychiatry

Volume number :

86

Pages :

1337-1346

Publication date :

2015-12-01

ISSN :

0022-3050

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

OBJECTIVE: Mutations in one of the 3 genes encoding collagen VI (COLVI) are responsible for a group of heterogeneous phenotypes of which Bethlem myopathy (BM) represents the milder end of the spectrum. Genotype-phenotype ...
Show more >OBJECTIVE: Mutations in one of the 3 genes encoding collagen VI (COLVI) are responsible for a group of heterogeneous phenotypes of which Bethlem myopathy (BM) represents the milder end of the spectrum. Genotype-phenotype correlations and long-term follow-up description in BM remain scarce. METHODS: We retrospectively evaluated the long-term clinical evolution, and genotype-phenotype correlations in 35 genetically identified BM patients (23 index cases). RESULTS: Nineteen patients showed a typical clinical picture with contractures, proximal weakness and slow disease progression while 11 presented a more severe evolution. Five patients showed an atypical presentation, namely a limb girdle muscle weakness in 2 and a congenital myopathy pattern with either no contractures, or only limited to ankles, in 3 of them. Pathogenic COL6A1-3 mutations were mostly missense or in frame exon-skipping resulting in substitutions or deletions. Twenty one different mutations were identified including 12 novel ones. The mode of inheritance was, autosomal dominant in 83% of the index patients (including 17% (N=4) with a de novo mutation), recessive in 13%, and undetermined in one patient. Skipping of exon 14 of COL6A1 was found in 35% of index cases and was mostly associated with a severe clinical evolution. Missense mutations were detected in 39% of index cases and associated with milder forms of the disease. CONCLUSIONS: Long-term follow-up identified important phenotypic variability in this cohort of 35 BM patients. However, worsening of the functional disability appeared typically after the age of 40 in 47% of our patients, and was frequently associated with COL6A1 exon 14 skipping.Show less >

Language :

Anglais

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 :

2019-09-24T10:01:59Z