A case report of recessive restrictive cardiomyopathy caused by a novel mutation in cardiac troponin I (TNNI3)

Malena P Pantou; Polyxeni Gourzi; Aggeliki Gkouziouta; Iakovos Armenis; Loukas Kaklamanis; Christianna Zygouri; Pantelis Constantoulakis; Stamatis Adamopoulos; Dimitrios Degiannis

doi:10.1186/s12881-019-0793-z

A case report of recessive restrictive cardiomyopathy caused by a novel mutation in cardiac troponin I (TNNI3)

BMC Med Genet. 2019 Apr 5;20(1):61. doi: 10.1186/s12881-019-0793-z.

Authors

Malena P Pantou¹, Polyxeni Gourzi², Aggeliki Gkouziouta³, Iakovos Armenis³, Loukas Kaklamanis⁴, Christianna Zygouri⁵, Pantelis Constantoulakis⁵, Stamatis Adamopoulos³, Dimitrios Degiannis¹

Affiliations

¹ Molecular Immunopathology and Histocompatibility Unit, Division of Genetics, Onassis Cardiac Surgery Center, Syggrou Av, 356, 176 74, Athens, Greece.
² Molecular Immunopathology and Histocompatibility Unit, Division of Genetics, Onassis Cardiac Surgery Center, Syggrou Av, 356, 176 74, Athens, Greece. gourzi@ocsc.gr.
³ Heart Failure, MCS and Transplant Unit, Onassis Cardiac Surgery Center, Athens, Greece.
⁴ Department of Pathology, Onassis Cardiac Surgery Center, Athens, Greece.
⁵ Department of Molecular Genetics, BioAnalytica-Genotypes S.A, Athens, Greece.

Abstract

Background: Restrictive cardiomyopathy is a rare cardiac disease, for which several genes including TNNT2, MYPN, FLNC and TNNI3 have been associated with its familial form.

Case presentation: Here we describe a female proband with a severely manifested restrictive phenotype leading to heart transplantation at the age of 41, who was found homozygous for the novel TNNI3 mutation: NM_000363.4:c.586G > C, p.(Asp196His). Her parents were third-degree cousins originating from a small village and although they were found heterozygous for the same variant they displayed no symptoms of the disease. Her older sister who was also found heterozygous was asymptomatic. Her twin sister and her brother who were homozygous for the same variant displayed a restrictive and a hypertrophic phenotype, respectively. Their children are all carriers of the mutation and remain asymptomatic until the age of 21.

Conclusion: These observations point to a recessive mode of inheritance reported for the first time for this combination of gene/disease.

Keywords: Autosomal recessive; Cardiac troponin I; Case report; Mutation; Restrictive cardiomyopathy; TNNI3.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cardiomyopathies / genetics*
Female
Genes, Recessive*
Genotype
Humans
Male
Mutation*
Pedigree
Troponin I / genetics*

Substances

Troponin I