Tags

Type your tag names separated by a space and hit enter

Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism?
Neurology. 2007 May 29; 68(22):1883-94.Neur

Abstract

BACKGROUND

Mutations in the EMD and LMNA genes, encoding emerin and lamins A and C, are responsible for the X-linked and autosomal dominant and recessive forms of Emery-Dreifuss muscular dystrophy (EDMD). LMNA mutations can also lead to several other disorders, collectively termed laminopathies, involving heart, fat, nerve, bone, and skin tissues, and some premature ageing syndromes.

METHODS

Fourteen members of a single family underwent neurologic, electromyographic, and cardiologic assessment. Gene mutation and protein expression analyses were performed for lamins A/C and emerin.

RESULTS

Clinical investigations showed various phenotypes, including isolated cardiac disease (seven patients), axonal neuropathy (one patient), and a combination of EDMD with axonal neuropathy (two patients), whereas five subjects remained asymptomatic. Genetic analyses identified the coincidence of a previously described homozygous LMNA mutation (c.892C-->T, p. R298C) and a new in-frame EMD deletion (c.110-112delAGA, p. delK37), which segregate independently. Analyses of the contribution of these mutations showed 1) the EMD codon deletion acts in X-linked dominant fashion and was sufficient to induce the cardiac disease, 2) the combination of both the hemizygous EMD and the homozygous LMNA mutations was necessary to induce the EDMD phenotype, 3) emerin was present in reduced amount in EMD-mutated cells, and 4) lamin A/C and emerin expression was most dramatically affected in the doubly mutated fibroblasts.

CONCLUSIONS

This highlights the crucial role of lamin A/C-emerin interactions, with evidence for synergistic effects of these mutations that lead to Emery-Dreifuss muscular dystrophy as the worsened result of digenic mechanism in this family.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale, Unité 582, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17536044

Citation

Ben Yaou, R, et al. "Multitissular Involvement in a Family With LMNA and EMD Mutations: Role of Digenic Mechanism?" Neurology, vol. 68, no. 22, 2007, pp. 1883-94.
Ben Yaou R, Toutain A, Arimura T, et al. Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism? Neurology. 2007;68(22):1883-94.
Ben Yaou, R., Toutain, A., Arimura, T., Demay, L., Massart, C., Peccate, C., Muchir, A., Llense, S., Deburgrave, N., Leturcq, F., Litim, K. E., Rahmoun-Chiali, N., Richard, P., Babuty, D., Récan-Budiartha, D., & Bonne, G. (2007). Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism? Neurology, 68(22), 1883-94.
Ben Yaou R, et al. Multitissular Involvement in a Family With LMNA and EMD Mutations: Role of Digenic Mechanism. Neurology. 2007 May 29;68(22):1883-94. PubMed PMID: 17536044.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism? AU - Ben Yaou,R, AU - Toutain,A, AU - Arimura,T, AU - Demay,L, AU - Massart,C, AU - Peccate,C, AU - Muchir,A, AU - Llense,S, AU - Deburgrave,N, AU - Leturcq,F, AU - Litim,K E, AU - Rahmoun-Chiali,N, AU - Richard,P, AU - Babuty,D, AU - Récan-Budiartha,D, AU - Bonne,G, PY - 2007/5/31/pubmed PY - 2007/7/13/medline PY - 2007/5/31/entrez SP - 1883 EP - 94 JF - Neurology JO - Neurology VL - 68 IS - 22 N2 - BACKGROUND: Mutations in the EMD and LMNA genes, encoding emerin and lamins A and C, are responsible for the X-linked and autosomal dominant and recessive forms of Emery-Dreifuss muscular dystrophy (EDMD). LMNA mutations can also lead to several other disorders, collectively termed laminopathies, involving heart, fat, nerve, bone, and skin tissues, and some premature ageing syndromes. METHODS: Fourteen members of a single family underwent neurologic, electromyographic, and cardiologic assessment. Gene mutation and protein expression analyses were performed for lamins A/C and emerin. RESULTS: Clinical investigations showed various phenotypes, including isolated cardiac disease (seven patients), axonal neuropathy (one patient), and a combination of EDMD with axonal neuropathy (two patients), whereas five subjects remained asymptomatic. Genetic analyses identified the coincidence of a previously described homozygous LMNA mutation (c.892C-->T, p. R298C) and a new in-frame EMD deletion (c.110-112delAGA, p. delK37), which segregate independently. Analyses of the contribution of these mutations showed 1) the EMD codon deletion acts in X-linked dominant fashion and was sufficient to induce the cardiac disease, 2) the combination of both the hemizygous EMD and the homozygous LMNA mutations was necessary to induce the EDMD phenotype, 3) emerin was present in reduced amount in EMD-mutated cells, and 4) lamin A/C and emerin expression was most dramatically affected in the doubly mutated fibroblasts. CONCLUSIONS: This highlights the crucial role of lamin A/C-emerin interactions, with evidence for synergistic effects of these mutations that lead to Emery-Dreifuss muscular dystrophy as the worsened result of digenic mechanism in this family. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/17536044/Multitissular_involvement_in_a_family_with_LMNA_and_EMD_mutations:_Role_of_digenic_mechanism L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=17536044 DB - PRIME DP - Unbound Medicine ER -