Hypertrophic cardiomyopathy: two homozygous cases with "typical" hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy

Luisa Nanni; Maurizio Pieroni; Cristina Chimenti; Barbara Simionati; Rosanna Zimbello; Attilio Maseri; Andrea Frustaci; Gerolamo Lanfranchi

doi:10.1016/j.bbrc.2003.08.014

Hypertrophic cardiomyopathy: two homozygous cases with "typical" hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy

Biochem Biophys Res Commun. 2003 Sep 19;309(2):391-8. doi: 10.1016/j.bbrc.2003.08.014.

Authors

Luisa Nanni¹, Maurizio Pieroni, Cristina Chimenti, Barbara Simionati, Rosanna Zimbello, Attilio Maseri, Andrea Frustaci, Gerolamo Lanfranchi

Affiliation

¹ CRIBI Biotechnology Center, Università degli Studi di Padova, Padua, Italy.

PMID: 12951062
DOI: 10.1016/j.bbrc.2003.08.014

Abstract

About 10% of cases of hypertrophic cardiomyopathy (HCM) evolve into dilated cardiomyopathy (DCM) with unknown causes. We studied 11 unrelated patients (pts) with HCM who progressed to DCM (group A) and 11 who showed "typical" HCM (group B). Mutational analysis of the beta-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), and cardiac troponin T (TNNT2) genes demonstrated eight mutations affecting MYH7 or MYBPC3 gene, five of which were new mutations. In group A-pts, the first new mutation occurred in the myosin head-rod junction and the second occurred in the light chain-binding site. The third new mutation leads to a MYBPC3 lacking titin and myosin binding sites. In group B, two pts with severe HCM carried two homozygous MYBPC3 mutations and one with moderate hypertrophy was a compound heterozygous for MYBPC3 gene. We identified five unreported mutations, potentially "malignant" defects as for the associated phenotypes, but no specific mutations of HCM/DCM.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Amino Acid Sequence
Cardiomyopathy, Dilated / classification*
Cardiomyopathy, Dilated / diagnosis
Cardiomyopathy, Dilated / genetics*
Cardiomyopathy, Hypertrophic, Familial / classification*
Cardiomyopathy, Hypertrophic, Familial / diagnosis
Cardiomyopathy, Hypertrophic, Familial / genetics*
Carrier Proteins / blood
Carrier Proteins / genetics
Carrier Proteins / metabolism
DNA Mutational Analysis / methods*
Female
Genetic Predisposition to Disease / genetics*
Homozygote
Humans
Male
Middle Aged
Molecular Sequence Data
Muscle Proteins / genetics*
Muscle Proteins / metabolism
Mutation
Sequence Alignment
Sequence Analysis, Protein
Troponin T / blood
Troponin T / genetics
Troponin T / metabolism
Ventricular Myosins / blood
Ventricular Myosins / genetics
Ventricular Myosins / metabolism

Substances

Carrier Proteins
Muscle Proteins
Troponin T
myosin-binding protein C
Ventricular Myosins