The proband (patient II2, Fig. 1a) was referred to our hospital at the age of 41
Case#:52 year old female from a small mountainous village in Peloponnese, Greece
DiseaseAssertion:severely manifested phenotype of RCM leading to heart transplant at 41
FamilyInfo:Family Pedigree Figure 1.Parents were third-degree cousins from the same village and were heterozygous for the same variant but displayed no symptoms of the disease. The older sister who was also found heterozygous was asymptomatic. Twin sister and brother were homozygous for the same variant and displayed a restrictive and a hypertrophic phenotype, respectively. Their children are all carriers of the mutation and remain asymptomatic until the age of 21
ParentalTesting:Family of the proband had Electrocardiogram and Doppler Echocardiogram (shown in figure 2) as well as TNNI3 genetic testing by targeted Sanger sequencing for the detection of the variant. Her twin sister and her brother were found homozygous for the variant, while both parents and the older sister were found heterozygous.
CasePresentingHPOs:HP:0002875, HP:0004757
CaseNotHPOFreeText:normal left ventricular dimensions
CasePreviousTesting:electrocardiogram, Right heart catheterization
Genotyping Method:NGS (filtered using VariantStudio Data Analysis Software and the Sophia Genetics DDM platform)
FunctionalAnalysis: a novel homozygous TNNI3 variant
Variant:NM_000363.4:c.586G > C, p.(Asp196His)
ClinVar:2169619
CAID:CA407439559