Linkage/Locus Report


Title: Linkage of familial dilated cardiomyopathy to chromosome 9.
Authors: Krajinovic M, Pinamonti B, Sinagra G, Vatta M, Severini GM, Milasin J, Falaschi A, Camerini F, Giacca M, and Mestroni L
Journal: Am J Hum Genet, 1995;57:846-852.
International Centre for Genetic Engineering and Biotechnology, Ospedale Maggiore, Trieste, Italy.
PubMed Link: 7573045
Citation Type: phenotype/genotype (clinical and genetic linkage data)
Study Design: family linkage study
Study Measurements: Study measurements:
Summary: In October, 1995 Luisa Mestroni and her group in Trieste reported a large Italian family with autosomal dominant FDC (and subsequently two smaller Italian families) identified clinically by left ventricular dimensions and function (20).  A diagnosis of dilated cardiomyopathy was made by the presence of both (1) an ejection fraction <0.45 by echocardiographic or radionuclide examination, and/or an M-mode echo fractional shortening less than 30%, and (2) a left ventricular end diastolic dimension (LVEDD) > 2.7 cm/m2, excluding any known cause of myocardial disease. Eighty family members were identified in 1987, and 13 were considered to be affected. Linkage was established for chromosome 9q13-q22 with a maximum multipoint lod score of 4.2, with the locus placed between D9S153 and D9S152.  The investigators observed concordance of genetic linkage data when retrospectively compared to data from subjects with a normal ejection fraction but enlarged left ventricular end-diastolic dimensions by echocardiography.
Comment: This was one of the earliest linkage reports of DCM from a carefully characterized kindred.



Linkage/Locus Report


Title: Gene mapping of familial autosomal dominant dilated cardiomyopathy to chromosome 10q21-23.
Authors: Bowles KR, Gajarski R, Porter P, Goytia V, Bachinski L, Roberts R, Pignatelli R, and Towbin JA.
Journal: J Clin Invest, 1996;96:1355-1360.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
PubMed Link: 8823300
Citation Type: phenotype/genotype (clinical and genetic data)
Study Design: family linkage study
Study Measurements:
Summary: 12 of 26 family members were affected with dilated cardiomyopathy consistent with autosomal dominant inheritance. Linkage was found to chromosome 10 (q21-q23). Eight of the 12 affected members demonstrated mitral valve prolapse and mitral regurgitation, a distinctive clinical marker. Linkage analysis provided a maximum lod score of 3.77 for the 10q21-q23 chromosomal region.


Autosomal Recessive (AR) Familial Dilated Cardiomyopathy.

One gene has been described in AR FDC, as described in the first report below. One additional clinical report has been included of AR FDC.

Cardiac Troponin I. TNNI3. Cardiac troponin I is one of the three components that form the troponin complex in the thin filaments of striated muscle (the others being troponins T and C).


Title. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy.

Authors. Murphy RT, Mogensen J, Shaw A, Kubo T, Hughes S, McKenna WJ.

Journal. Lancet 2004;363:371-2.

Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK.

PMID: 15070570

Citation type: phenotype/genotype (clinical and genetic data)

Study design: mutation screening of patients with IDC

Study measurements:

Study Summary: Variations in the sequence of the cardiac troponin I (TNNI3) gene were examined in 235 patients with dilated cardiomyopathy. One mutation was identified in a family with recessive disease.

Comment: The McKenna group at St George’s Hospital again contributed to the genetic cardiomyopathy literature with this first report of recessive DCM.

Title. Evidence for autosomal recessive inheritance of infantile dilated cardiomyopathy: studies from the Eastern Province of Saudi Arabia. Authors. Seliem MA, Mansara KB, Palileo M, Ye X, Zhang Z, Benson DW.

Journal. Pediatr Res 2000;48:770-5

Specialty Pediatrics Division, Saudi Aramco-Dhahran Health Center, Dhahran 31311, Saudi Arabia.

PMID: 11102545

This was a study of 55 pediatric patients all less than 10 years of age with dilated cardiomyopathy from 41 families of Arab descent. The patient cohort represented 20% of the total number of children from these families. In 19 families parents were first cousins. Complex segregation analysis suggested a recessive inheritance model.