PMID- 10323252
OWN - NLM
STAT- MEDLINE
DCOM- 19990521
LR  - 20190722
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 104
IP  - 3
DP  - 1999 Mar
TI  - Changes at P183 of emerin weaken its protein-protein interactions resulting in
      X-linked Emery-Dreifuss muscular dystrophy.
PG  - 262-8
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive muscular
      dystrophy characterized by early contractures of the elbows, Achilles tendons and
      spine, slowly progressive muscle wasting and weakness, and cardiomyopathy
      associated with cardiac conduction defects. The emerin gene has been mapped to
      Xq28 and encodes a 34-kDa serine-rich protein, emerin, which has been localized
      to the nuclear envelope in a wide variety of tissues, including skeletal and
      cardiac muscle. Mutations spanning the emerin gene have been identified in
      patients with EDMD. We present here the effect, on emerin protein expression, of 
      two missense mutations identified in unrelated EDMD patients. These alterations
      predict the replacement of a proline residue at position 183 with either a
      histidine or a threonine. Biochemical analysis has demonstrated that the mobility
      and expression levels of the mutant forms of emerin are indistinguishable from
      that of wild-type emerin, but that they have weakened interactions with nuclear
      lamina components. In comparison with the usual EDMD phenotype, patients with
      P183 missense mutations have a later age at onset of first symptoms, elbow
      contractures, ankle contractures, upper limb weakness and lower limb weakness,
      but there is no difference for the age at onset of cardiac involvement. This is
      the first report of protein studies on patients with missense mutations resulting
      in the clinical features of EDMD. These studies demonstrate the importance of
      proline 183 for the proper structure/function of emerin.
FAU - Ellis, J A
AU  - Ellis JA
AD  - Department of Medical Genetics, University of Cambridge, Cambridge Institute for 
      Medical Research, Addenbrooke's Hospital, UK.
FAU - Yates, J R
AU  - Yates JR
FAU - Kendrick-Jones, J
AU  - Kendrick-Jones J
FAU - Brown, C A
AU  - Brown CA
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Thymopoietins)
RN  - 0 (emerin)
RN  - 9DLQ4CIU6V (Proline)
SB  - IM
MH  - Adult
MH  - Amino Acid Substitution
MH  - Cell Line, Transformed
MH  - DNA Mutational Analysis
MH  - Genetic Linkage
MH  - Genotype
MH  - Humans
MH  - Immunoblotting
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism
MH  - Membranes/metabolism
MH  - Muscular Dystrophies/*genetics
MH  - Muscular Dystrophy, Emery-Dreifuss
MH  - Mutation
MH  - Nuclear Proteins
MH  - Phenotype
MH  - Phosphorylation
MH  - Proline/*genetics
MH  - Protein Binding
MH  - Thymopoietins/*genetics/metabolism
MH  - X Chromosome/*genetics
EDAT- 1999/05/14 00:00
MHDA- 1999/05/14 00:01
CRDT- 1999/05/14 00:00
PHST- 1999/05/14 00:00 [pubmed]
PHST- 1999/05/14 00:01 [medline]
PHST- 1999/05/14 00:00 [entrez]
AID - 10.1007/s004390050946 [doi]
PST - ppublish
SO  - Hum Genet. 1999 Mar;104(3):262-8. doi: 10.1007/s004390050946.