PMID- 10430757
OWN - NLM
STAT- MEDLINE
DCOM- 19990813
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 100
IP  - 5
DP  - 1999 Aug 3
TI  - Desmin mutation responsible for idiopathic dilated cardiomyopathy.
PG  - 461-4
AB  - BACKGROUND: Idiopathic dilated cardiomyopathy, of which approximately 20% of
      cases are familial (FDCM), is a primary myocardial disorder characterized by
      ventricular dilatation and impaired systolic function. It is a common cause of
      heart failure and the need for cardiac transplantation. Although 6 chromosomal
      loci responsible for autosomal dominant FDCM have been mapped by linkage
      analysis, none of these genes have been identified. By use of the candidate-gene 
      approach, actin was identified recently as being responsible for dilated
      cardiomyopathy. Considerable evidence suggests desmin, a muscle-specific
      intermediate filament, plays a significant role in cardiac growth and
      development. METHODS AND RESULTS: To determine whether a defect of desmin induces
      dilated cardiomyopathy, 44 probands with FDCM underwent clinical evaluation and
      DNA analysis. Diagnostic criteria, detected by echocardiography, consisted of
      ventricular dimension of >/=2.7 cm/m(2) with an ejection fraction </=50% in the
      absence of other potential causes. After amplification by polymerase chain
      reaction, the exons of the desmin gene were sequenced. A missense desmin
      mutation, Ile451Met, which cosegregates with FDCM without clinically evident
      skeletal muscle abnormalities, was identified in a 4-generation family but was
      not detected in 460 unrelated healthy individuals. CONCLUSIONS: A novel missense 
      mutation of desmin, Ile451Met, was identified as the genetic cause of idiopathic 
      dilated cardiomyopathy. This finding is of particular significance because this
      is the first mutation detected in the desmin tail domain, and the function of the
      desmin tail remains unknown. Because this mutation leads to a restricted cardiac 
      phenotype in the family studied in the present report, it suggests that the tail 
      of desmin plays an important functional role in cardiac tissue.
FAU - Li, D
AU  - Li D
AD  - Section of Cardiology, Molecular Biology Computational Resource, Baylor College
      of Medicine, Houston, TX, USA.
FAU - Tapscoft, T
AU  - Tapscoft T
FAU - Gonzalez, O
AU  - Gonzalez O
FAU - Burch, P E
AU  - Burch PE
FAU - Quinones, M A
AU  - Quinones MA
FAU - Zoghbi, W A
AU  - Zoghbi WA
FAU - Hill, R
AU  - Hill R
FAU - Bachinski, L L
AU  - Bachinski LL
FAU - Mann, D L
AU  - Mann DL
FAU - Roberts, R
AU  - Roberts R
LA  - eng
GR  - P50-HL54313/HL/NHLBI NIH HHS/United States
GR  - T32-HLO7706/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (DNA Primers)
RN  - 0 (Desmin)
SB  - IM
CIN - Circulation. 2000 Sep 26;102(13):E100-1. PMID: 11004158
MH  - Cardiomyopathy, Dilated/*genetics
MH  - DNA Primers
MH  - Desmin/*genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - *Mutation, Missense
MH  - Pedigree
MH  - Sequence Analysis, DNA
EDAT- 1999/08/03 00:00
MHDA- 1999/08/03 00:01
CRDT- 1999/08/03 00:00
PHST- 1999/08/03 00:00 [pubmed]
PHST- 1999/08/03 00:01 [medline]
PHST- 1999/08/03 00:00 [entrez]
AID - 10.1161/01.cir.100.5.461 [doi]
PST - ppublish
SO  - Circulation. 1999 Aug 3;100(5):461-4. doi: 10.1161/01.cir.100.5.461.