Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy

Jinong Feng, Jin Yan, Carolyn H. Buzin, Jeffrey Towbin, Steve S. Sommer

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Dilated cardiomyopathy (DCM) is the major indication for heart transplantation. Approximately 30% of all DCM is thought to be inherited, while 70% is sporadic. Mutations in the dystrophin gene have been associated with the uncommon X-linked form of DCM. We hypothesized that missense mutations and other less severe mutations of the dystrophin gene might predispose to the common form of sporadic DCM. To test this hypothesis, 22 kb of genomic dystrophin DNA was scanned with DOVAM-S in each of the 22 patients with sporadic DCM, including all 79 coding sequences and splice junctions, as well as six alternative exon 1 dystrophin isoforms (484 kb, total). Three putative new mutations (IVS5 +1 G > T, K18N, and F3228L) and seven polymorphisms were identified. The splice site mutation IVS5 + 1 is predicted to cause skipping of exon 5, which is within a region containing an actin binding site. The missense mutations occur at amino acids that display substantial evolutionary conservation. Screening of 236 control individuals failed to identify these three mutations. The three patients with putative mutations had CK-MM (creatine kinase, skeletal muscle) levels greater than 250 units while the 14 patients without mutations for which CK-MM were available had values ranging from 20 to 200. The first comprehensive mutation scanning of the exons and splice junctions of the dystrophin gene in patients with sporadic DCM presents the evidence that point mutations are associated with sporadic DCM without clinical evidence of skeletal myopathy. It may be prudent to measure CK-MM in all patients with dilated cardiomyopathy to identify candidates at high risk for dystrophin mutations.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalMolecular Genetics and Metabolism
Volume77
Issue number1-2
DOIs
StatePublished - Oct 29 2002
Externally publishedYes

Fingerprint

Dystrophin
Dilated Cardiomyopathy
Genes
Mutation
Exons
MM Form Creatine Kinase
Missense Mutation
Polymorphism
Muscle
Actins
Conservation
Screening
Protein Isoforms
Binding Sites
Muscular Diseases
Heart Transplantation
Scanning
Point Mutation
Amino Acids
DNA

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy. / Feng, Jinong; Yan, Jin; Buzin, Carolyn H.; Towbin, Jeffrey; Sommer, Steve S.

In: Molecular Genetics and Metabolism, Vol. 77, No. 1-2, 29.10.2002, p. 119-126.

Research output: Contribution to journalArticle

Feng, Jinong ; Yan, Jin ; Buzin, Carolyn H. ; Towbin, Jeffrey ; Sommer, Steve S. / Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy. In: Molecular Genetics and Metabolism. 2002 ; Vol. 77, No. 1-2. pp. 119-126.
@article{d1c1d5bef8844c3b8ebe67ece112f8d7,
title = "Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy",
abstract = "Dilated cardiomyopathy (DCM) is the major indication for heart transplantation. Approximately 30{\%} of all DCM is thought to be inherited, while 70{\%} is sporadic. Mutations in the dystrophin gene have been associated with the uncommon X-linked form of DCM. We hypothesized that missense mutations and other less severe mutations of the dystrophin gene might predispose to the common form of sporadic DCM. To test this hypothesis, 22 kb of genomic dystrophin DNA was scanned with DOVAM-S in each of the 22 patients with sporadic DCM, including all 79 coding sequences and splice junctions, as well as six alternative exon 1 dystrophin isoforms (484 kb, total). Three putative new mutations (IVS5 +1 G > T, K18N, and F3228L) and seven polymorphisms were identified. The splice site mutation IVS5 + 1 is predicted to cause skipping of exon 5, which is within a region containing an actin binding site. The missense mutations occur at amino acids that display substantial evolutionary conservation. Screening of 236 control individuals failed to identify these three mutations. The three patients with putative mutations had CK-MM (creatine kinase, skeletal muscle) levels greater than 250 units while the 14 patients without mutations for which CK-MM were available had values ranging from 20 to 200. The first comprehensive mutation scanning of the exons and splice junctions of the dystrophin gene in patients with sporadic DCM presents the evidence that point mutations are associated with sporadic DCM without clinical evidence of skeletal myopathy. It may be prudent to measure CK-MM in all patients with dilated cardiomyopathy to identify candidates at high risk for dystrophin mutations.",
author = "Jinong Feng and Jin Yan and Buzin, {Carolyn H.} and Jeffrey Towbin and Sommer, {Steve S.}",
year = "2002",
month = "10",
day = "29",
doi = "10.1016/S1096-7192(02)00153-1",
language = "English (US)",
volume = "77",
pages = "119--126",
journal = "Molecular Genetics and Metabolism",
issn = "1096-7192",
publisher = "Academic Press Inc.",
number = "1-2",

}

TY - JOUR

T1 - Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy

AU - Feng, Jinong

AU - Yan, Jin

AU - Buzin, Carolyn H.

AU - Towbin, Jeffrey

AU - Sommer, Steve S.

PY - 2002/10/29

Y1 - 2002/10/29

N2 - Dilated cardiomyopathy (DCM) is the major indication for heart transplantation. Approximately 30% of all DCM is thought to be inherited, while 70% is sporadic. Mutations in the dystrophin gene have been associated with the uncommon X-linked form of DCM. We hypothesized that missense mutations and other less severe mutations of the dystrophin gene might predispose to the common form of sporadic DCM. To test this hypothesis, 22 kb of genomic dystrophin DNA was scanned with DOVAM-S in each of the 22 patients with sporadic DCM, including all 79 coding sequences and splice junctions, as well as six alternative exon 1 dystrophin isoforms (484 kb, total). Three putative new mutations (IVS5 +1 G > T, K18N, and F3228L) and seven polymorphisms were identified. The splice site mutation IVS5 + 1 is predicted to cause skipping of exon 5, which is within a region containing an actin binding site. The missense mutations occur at amino acids that display substantial evolutionary conservation. Screening of 236 control individuals failed to identify these three mutations. The three patients with putative mutations had CK-MM (creatine kinase, skeletal muscle) levels greater than 250 units while the 14 patients without mutations for which CK-MM were available had values ranging from 20 to 200. The first comprehensive mutation scanning of the exons and splice junctions of the dystrophin gene in patients with sporadic DCM presents the evidence that point mutations are associated with sporadic DCM without clinical evidence of skeletal myopathy. It may be prudent to measure CK-MM in all patients with dilated cardiomyopathy to identify candidates at high risk for dystrophin mutations.

AB - Dilated cardiomyopathy (DCM) is the major indication for heart transplantation. Approximately 30% of all DCM is thought to be inherited, while 70% is sporadic. Mutations in the dystrophin gene have been associated with the uncommon X-linked form of DCM. We hypothesized that missense mutations and other less severe mutations of the dystrophin gene might predispose to the common form of sporadic DCM. To test this hypothesis, 22 kb of genomic dystrophin DNA was scanned with DOVAM-S in each of the 22 patients with sporadic DCM, including all 79 coding sequences and splice junctions, as well as six alternative exon 1 dystrophin isoforms (484 kb, total). Three putative new mutations (IVS5 +1 G > T, K18N, and F3228L) and seven polymorphisms were identified. The splice site mutation IVS5 + 1 is predicted to cause skipping of exon 5, which is within a region containing an actin binding site. The missense mutations occur at amino acids that display substantial evolutionary conservation. Screening of 236 control individuals failed to identify these three mutations. The three patients with putative mutations had CK-MM (creatine kinase, skeletal muscle) levels greater than 250 units while the 14 patients without mutations for which CK-MM were available had values ranging from 20 to 200. The first comprehensive mutation scanning of the exons and splice junctions of the dystrophin gene in patients with sporadic DCM presents the evidence that point mutations are associated with sporadic DCM without clinical evidence of skeletal myopathy. It may be prudent to measure CK-MM in all patients with dilated cardiomyopathy to identify candidates at high risk for dystrophin mutations.

UR - http://www.scopus.com/inward/record.url?scp=0036396662&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036396662&partnerID=8YFLogxK

U2 - 10.1016/S1096-7192(02)00153-1

DO - 10.1016/S1096-7192(02)00153-1

M3 - Article

VL - 77

SP - 119

EP - 126

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 1-2

ER -