PMID- 10080180
OWN - NLM
STAT- MEDLINE
DCOM- 19990331
LR  - 20220408
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 21
IP  - 3
DP  - 1999 Mar
TI  - Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss 
      muscular dystrophy.
PG  - 285-8
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures
      of elbows and Achilles tendons, slowly progressive muscle wasting and weakness,
      and a cardiomyopathy with conduction blocks which is life-threatening. Two modes 
      of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD;
      OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the
      disease. Mutations in EMD, the gene encoding emerin, are responsible for the
      X-linked form. We have mapped the locus for EDMD-AD to an 8-cM interval on
      chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype 
      in four other small families was potentially linked to this locus. This region
      contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the
      nuclear lamina, lamins A and C, produced by alternative splicing. We identified
      four mutations in LMNA that co-segregate with the disease phenotype in the five
      families: one nonsense mutation and three missense mutations. These results are
      the first identification of mutations in a component of the nuclear lamina as a
      cause of inherited muscle disorder. Together with mutations in EMD (refs 5,6),
      they underscore the potential importance of the nuclear envelope components in
      the pathogenesis of neuromuscular disorders.
FAU - Bonne, G
AU  - Bonne G
AD  - INSERM UR153, GH Pitie-Salpetriere, Paris, France.gbonne@myologie.infobiogen.fr
FAU - Di Barletta, M R
AU  - Di Barletta MR
FAU - Varnous, S
AU  - Varnous S
FAU - Becane, H M
AU  - Becane HM
FAU - Hammouda, E H
AU  - Hammouda EH
FAU - Merlini, L
AU  - Merlini L
FAU - Muntoni, F
AU  - Muntoni F
FAU - Greenberg, C R
AU  - Greenberg CR
FAU - Gary, F
AU  - Gary F
FAU - Urtizberea, J A
AU  - Urtizberea JA
FAU - Duboc, D
AU  - Duboc D
FAU - Fardeau, M
AU  - Fardeau M
FAU - Toniolo, D
AU  - Toniolo D
FAU - Schwartz, K
AU  - Schwartz K
LA  - eng
SI  - GENBANK/L12399
SI  - GENBANK/L12400
SI  - GENBANK/L12401
SI  - GENBANK/O03252
SI  - GENBANK/P02545
SI  - GENBANK/P02546
SI  - GENBANK/P08928
SI  - GENBANK/P09010
SI  - GENBANK/P11048
SI  - GENBANK/P11516
SI  - GENBANK/P13648
SI  - GENBANK/P14731
SI  - GENBANK/P14732
SI  - GENBANK/P14733
SI  - GENBANK/P20700
SI  - GENBANK/P21619
SI  - GENBANK/P21910
SI  - GENBANK/P48678
SI  - GENBANK/P48679
GR  - E.0297/TI_/Telethon/Italy
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Lamin Type A)
RN  - 0 (Lamins)
RN  - 0 (Nuclear Proteins)
RN  - EC 3.1.21.- (Deoxyribonuclease HpaII)
RN  - EC 3.1.21.4 (CTAG-specific type II deoxyribonucleases)
RN  - EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cloning, Molecular
MH  - Deoxyribonuclease HpaII/genetics
MH  - Deoxyribonucleases, Type II Site-Specific/genetics
MH  - Exons
MH  - Female
MH  - Genes, Dominant
MH  - Haplotypes
MH  - Humans
MH  - Immunohistochemistry
MH  - Lamin Type A
MH  - Lamins
MH  - Male
MH  - Microsatellite Repeats
MH  - Molecular Sequence Data
MH  - Muscular Dystrophies/*genetics
MH  - Muscular Dystrophy, Emery-Dreifuss
MH  - *Mutation
MH  - Myocardium/metabolism/pathology
MH  - Nuclear Proteins/analysis/*genetics/metabolism
MH  - Pedigree
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
EDAT- 1999/03/18 03:02
MHDA- 2001/03/23 10:01
CRDT- 1999/03/18 03:02
PHST- 1999/03/18 03:02 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/03/18 03:02 [entrez]
AID - 10.1038/6799 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Mar;21(3):285-8. doi: 10.1038/6799.