4 generations
Case#: Family 1, individual II-5
DiseaseAssertion: Dilated cardiomyopathy
FamilyInfo: The proband has a family history of DCM. His father and brother also had DCM and died from heart failure at ages 69 and 63 respectively. The disease follows an autosomal dominant inheritance pattern.
ParentalTesting: Want reported, his father had DMC but this article does not confirm genetic testing of his parents.
CasePresentingHPOs: Dilated cardiomyopathy (HP:0001644) & left ventricular systolic dysfunction (HP:0005162)
CaseHPOFreeText: The proband was diagnosed with DCM at age 45 and received medication for heart failure. At the time of the study he was 66 years old. His echocardiogram showed an enlarged left ventricle and reduced heart function with an ejection fraction of 33%.
CaseNotHPOs: NR
CaseNotHPOFreeText: The researchers reported no other structural heart diseases or conditions contributing to DCM in the affected family members, including coronary heart disease, valvular heart disease, viral myocarditis and hypertension.
CasePreviousTesting: ECG, clinical examination and routine laboratory testing were part of the study assessment. The probands echocardiogram showed a left ventricular end diastolic diameter of 63 mm and an ejection fraction of 33%.
Genotyping Method: Genome wide microsatellite screening, genetic linkage analysis, whole exome sequencing and sanger sequencing.
FunctionalAnalysis: Laboratory experiments showed that the KLF13 E144X mutation reduced the proteins ability to activate the heart related genes ACTC1 and MYH7. The mutation also affected DNA binding cooperation with GATA4 and normal nuclear localization.
Variant: KLF13 c.430G >T
Clinvar: NR
CAID: CA391891162
gnomAD: The researchers reported that the variant was absent from gnomAD and other population databases at the time of their study. No numerical allele frequency was provided.
AdditionalInfo: The proband is a male from a 4th generation Chinese family. His KLF13 mutation was associated with familial DCM. the researchers found that the mutation was shared by affected family members and was absent from unaffected family members and 418 unrelated healthy controls.