(Circulation. 2001;103:1256.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Novel Gene Mutations in Patients With Left Ventricular Noncompaction or Barth Syndrome
From the Department of Pediatrics, Toyama Medical and Pharmaceutical University, Toyama (F.I., S.T., K.U., T.M.), and Department of Pediatrics, Shimane Medical University (N.H.), Japan; the Departments of Molecular and Human Genetics (K.R.B., J.A.T.), Pediatrics (Cardiology) (W.J.D., H.L., N.E.B., J.A.T.), and Cardiovascular Sciences (J.A.T.), Baylor College of Medicine, Texas Children’s Hospital, Houston, Tex; and the Children’s Hospital at St Joseph’s, Paterson, NJ (J.M.).
Correspondence to Jeffrey A. Towbin, MD, Department of Pediatrics (Cardiology), Baylor College of Medicine, One Baylor Plaza, Room 333E, Houston, TX 77030. E-mail jtowbin{at}bcm.tmc.edu
Background—Mutations in the gene G4.5 result in a wide spectrum of severe infantile cardiomyopathic phenotypes, including isolated left ventricular noncompaction (LVNC), as well as Barth syndrome (BTHS) with dilated cardiomyopathy (DCM). The purpose of this study was to investigate patients with LVNC or BTHS for mutations in G4.5 or other novel genes.
Methods and Results—DNA
was isolated from 2 families and 3 individuals with isolated LVNC or
LVNC with congenital heart disease (CHD), as well as 4 families with
BTHS associated with LVNC or DCM, and screened for mutations by
single-strand DNA conformation polymorphism analysis and DNA
sequencing. In 1 family with LVNC and CHD, a C
T mutation was
identified at nucleotide 362 of
-dystrobrevin, changing a
proline to leucine (P121L). Mutations in
G4.5 were identified in 2
families with isolated LVNC: a missense mutation in exon 4 (C118R) in 1
and a splice donor mutation (IVS10+2TA) in intron 10 in the other.
In a family with cardiomyopathies ranging from BTHS or fatal infantile
cardiomyopathy to asymptomatic DCM, a splice acceptor mutation in exon
2 of G4.5 (398-2 AG) was
identified, and a 1-bp deletion in exon 2 of G4.5, resulting in a stop
codon after amino acid 41, was identified in a sporadic case of
BTHS.
Conclusions—These data
demonstrate genetic heterogeneity in LVNC, with mutation of a novel
gene, -dystrobrevin,
identified in LVNC associated with CHD. In addition, these results
confirm that mutations in G4.5
result in a wide phenotypic spectrum of
cardiomyopathies.
Key Words: cardiomyopathy • genetics • heart defects, congenital
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