PMID- 10508519
OWN - NLM
STAT- MEDLINE
DCOM- 19991019
LR  - 20061115
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 23
IP  - 2
DP  - 1999 Oct
TI  - Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy
      and nemaline myopathy.
PG  - 208-12
AB  - Muscle contraction results from the force generated between the thin filament
      protein actin and the thick filament protein myosin, which causes the thick and
      thin muscle filaments to slide past each other. There are skeletal muscle,
      cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin.
      Inherited diseases in humans have been associated with defects in cardiac actin
      (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin
      (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report
      that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are
      associated with two different muscle diseases, 'congenital myopathy with excess
      of thin myofilaments' (actin myopathy) and nemaline myopathy. Both diseases are
      characterized by structural abnormalities of the muscle fibres and variable
      degrees of muscle weakness. We have identified 15 different missense mutations
      resulting in 14 different amino acid changes. The missense mutations in ACTA1 are
      distributed throughout all six coding exons, and some involve known functional
      domains of actin. Approximately half of the patients died within their first
      year, but two female patients have survived into their thirties and have
      children. We identified dominant mutations in all but 1 of 14 families, with the 
      missense mutations being single and heterozygous. The only family showing
      dominant inheritance comprised a 33-year-old affected mother and her two affected
      and two unaffected children. In another family, the clinically unaffected father 
      is a somatic mosaic for the mutation seen in both of his affected children. We
      identified recessive mutations in one family in which the two affected siblings
      had heterozygous mutations in two different exons, one paternally and the other
      maternally inherited. We also identified de novo mutations in seven sporadic
      probands for which it was possible to analyse parental DNA.
FAU - Nowak, K J
AU  - Nowak KJ
AD  - Centre for Neuromuscular Disorders, University of Western Australia, Nedlands,
      Western Australia 6009, Australia.
FAU - Wattanasirichaigoon, D
AU  - Wattanasirichaigoon D
FAU - Goebel, H H
AU  - Goebel HH
FAU - Wilce, M
AU  - Wilce M
FAU - Pelin, K
AU  - Pelin K
FAU - Donner, K
AU  - Donner K
FAU - Jacob, R L
AU  - Jacob RL
FAU - Hubner, C
AU  - Hubner C
FAU - Oexle, K
AU  - Oexle K
FAU - Anderson, J R
AU  - Anderson JR
FAU - Verity, C M
AU  - Verity CM
FAU - North, K N
AU  - North KN
FAU - Iannaccone, S T
AU  - Iannaccone ST
FAU - Muller, C R
AU  - Muller CR
FAU - Nurnberg, P
AU  - Nurnberg P
FAU - Muntoni, F
AU  - Muntoni F
FAU - Sewry, C
AU  - Sewry C
FAU - Hughes, I
AU  - Hughes I
FAU - Sutphen, R
AU  - Sutphen R
FAU - Lacson, A G
AU  - Lacson AG
FAU - Swoboda, K J
AU  - Swoboda KJ
FAU - Vigneron, J
AU  - Vigneron J
FAU - Wallgren-Pettersson, C
AU  - Wallgren-Pettersson C
FAU - Beggs, A H
AU  - Beggs AH
FAU - Laing, N G
AU  - Laing NG
LA  - eng
SI  - GENBANK/AF182035
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Actins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Actins/*genetics
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Base Sequence
MH  - Child
MH  - Child, Preschool
MH  - DNA/chemistry/genetics
MH  - DNA Mutational Analysis
MH  - Family Health
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Molecular Sequence Data
MH  - Muscle, Skeletal/*metabolism
MH  - Muscular Diseases/*genetics
MH  - Mutation
MH  - Myopathies, Nemaline/*genetics
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
EDAT- 1999/10/03 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/10/03 09:00
PHST- 1999/10/03 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/10/03 09:00 [entrez]
AID - 10.1038/13837 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Oct;23(2):208-12. doi: 10.1038/13837.