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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mutations of the FHL1 Gene Cause Emery-Dreifuss Muscular Dystrophy
American Journal of Human Genetics, Volume 85, No. 3, Year 2009
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Description
Emery-Dreifuss muscular dystrophy (EDMD) is a rare disorder characterized by early joint contractures, muscular dystrophy, and cardiac involvement with conduction defects and arrhythmias. So far, only 35% of EDMD cases are genetically elucidated and associated with EMD or LMNA gene mutations, suggesting the existence of additional major genes. By whole-genome scan, we identified linkage to the Xq26.3 locus containing the FHL1 gene in three informative families belonging to our EMD- and LMNA-negative cohort. Analysis of the FHL1 gene identified seven mutations, in the distal exons of FHL1 in these families, three additional families, and one isolated case, which differently affect the three FHL1 protein isoforms: two missense mutations affecting highly conserved cysteines, one abolishing the termination codon, and four out-of-frame insertions or deletions. The predominant phenotype was characterized by myopathy with scapulo-peroneal and/or axial distribution, as well as joint contractures, and associated with a peculiar cardiac disease characterized by conduction defects, arrhythmias, and hypertrophic cardiomyopathy in all index cases of the seven families. Heterozygous female carriers were either asymptomatic or had cardiac disease and/or mild myopathy. Interestingly, four of the FHL1-mutated male relatives had isolated cardiac disease, and an overt hypertrophic cardiomyopathy was present in two. Expression and functional studies demonstrated that the FHL1 proteins were severely reduced in all tested patients and that this was associated with a severe delay in myotube formation in the two patients for whom myoblasts were available. In conclusion, FHL1 should be considered as a gene associated with the X-linked EDMD phenotype, as well as with hypertrophic cardiomyopathy. © 2009 The American Society of Human Genetics.
Authors & Co-Authors
Gueneau, Lucie
France, Paris
Inserm
France, Paris
Sorbonne Université
Bertrand, Anne T.
France, Paris
Inserm
France, Paris
Sorbonne Université
Jaïs, Jean Philippe
France, Paris
Université Paris Cité
Salih, Mustafa Abdalla M.
Saudi Arabia, Riyadh
College of Medicine
Stojkovic, Tanya
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Wehnert, Manfred
Germany, Greifswald
Institute of Human Genetics
Hoeltzenbein, Maria
Germany, Greifswald
Institute of Human Genetics
Spuler, Simone
Germany, Berlin
Charité – Universitätsmedizin Berlin
Saitoh, Shinji
Japan, Sapporo
Graduate School of Medicine
Verschueren, Annie
France, Marseille
Hopital la Timone
Tranchant, Christine H.
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Beuvin, Maud
France, Paris
Inserm
France, Paris
Sorbonne Université
Lacene, Emmanuelle
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Roméro, Norma Beatriz
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Heath, Simon C.
France, Evry
Centre National de Recherche en Génomique Humaine
Zélénika, Diana
France, Evry
Centre National de Recherche en Génomique Humaine
Voit, Thomas
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Eymard, Bruno
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Ben Yaou, Rabah
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Bonne, Giséle
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Statistics
Citations: 212
Authors: 20
Affiliations: 11
Identifiers
Doi:
10.1016/j.ajhg.2009.07.015
ISSN:
00029297
Research Areas
Disability
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cohort Study
Participants Gender
Male
Female