Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.

J Mogensen; I C Klausen; A K Pedersen; H Egeblad; P Bross; Torben A Kruse; N Gregersen; P S Hansen; U Baandrup; A D Borglum

doi:10.1172/JCI6460

Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.

J Mogensen, I C Klausen, A K Pedersen, H Egeblad, P Bross, Torben A Kruse, N Gregersen, P S Hansen, U Baandrup, A D Borglum

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.

Original language	English
Journal	Journal of Clinical Investigation
Volume	103
Issue	10
Pages (from-to)	R39-43
ISSN	0021-9738
DOIs	https://doi.org/10.1172/JCI6460
Publication status	Published - 1999

Keywords

Actins
Adult
Aged
Aged, 80 and over
Base Sequence
Cardiomyopathy, Dilated
Cardiomyopathy, Hypertrophic
DNA Primers
Exons
Female
Humans
Linkage (Genetics)
Lod Score
Male
Middle Aged
Models, Molecular
Myocardial Contraction
Pedigree
Point Mutation
Protein Conformation

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@article{cb6baea0a02c11dd889c000ea68e967b,

title = "Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.",

abstract = "We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.",

keywords = "Actins, Adult, Aged, Aged, 80 and over, Base Sequence, Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic, DNA Primers, Exons, Female, Humans, Linkage (Genetics), Lod Score, Male, Middle Aged, Models, Molecular, Myocardial Contraction, Pedigree, Point Mutation, Protein Conformation",

author = "J Mogensen and Klausen, {I C} and Pedersen, {A K} and H Egeblad and P Bross and Kruse, {Torben A} and N Gregersen and Hansen, {P S} and U Baandrup and Borglum, {A D}",

year = "1999",

doi = "10.1172/JCI6460",

language = "English",

volume = "103",

pages = "R39--43",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

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TY - JOUR

T1 - Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.

AU - Mogensen, J

AU - Klausen, I C

AU - Pedersen, A K

AU - Egeblad, H

AU - Bross, P

AU - Kruse, Torben A

AU - Gregersen, N

AU - Hansen, P S

AU - Baandrup, U

AU - Borglum, A D

PY - 1999

Y1 - 1999

N2 - We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.

AB - We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.

KW - Actins

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Base Sequence

KW - Cardiomyopathy, Dilated

KW - Cardiomyopathy, Hypertrophic

KW - DNA Primers

KW - Exons

KW - Female

KW - Humans

KW - Linkage (Genetics)

KW - Lod Score

KW - Male

KW - Middle Aged

KW - Models, Molecular

KW - Myocardial Contraction

KW - Pedigree

KW - Point Mutation

KW - Protein Conformation

U2 - 10.1172/JCI6460

DO - 10.1172/JCI6460

M3 - Journal article

C2 - 10330430

SN - 0021-9738

VL - 103

SP - R39-43

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 10

ER -

Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.

Abstract

Keywords

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