H. Kokado et al., Clinical features of hypertrophic cardiomyopathy caused by a Lys183 deletion mutation in the cardiac troponin I gene, CIRCULATION, 102(6), 2000, pp. 663-669
Citations number
40
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-Mutations that cause hypertrophic cardiomyopathy (HCM) have been
identified in 9 genes that code proteins in the sarcomere, Previous report
s have demonstrated that cardiac troponin I (cTnI) gene mutations may accou
nt for familial HCM; however, the clinical characteristics and prognosis of
patients with HCM caused by cTnI gene mutations are not known.
Methods and Results-We analyzed cTnI gene mutations in 130 unrelated proban
ds with HCM and their families to clarify the genotype-phenotype correlatio
ns. We identified 25 individuals in 7 families with a Lys183 deletion (Lys1
83 del) mutation in exon 7 of the cTnI gene. The disease penetrance in subj
ects aged >20 years was 88% by echocardiography and 96% by EGG. Sudden deat
h occurred in 7 individuals of 4 families at any age. Overall, 7 (43.8%) of
16 individuals aged >40 years had left ventricular systolic dysfunction, a
nd 3 (18.8%) displayed dilated cardiomyopathy-like features. Of affected in
dividuals, 4 of 5 individuals aged >40 years followed by echocardiography s
howed septal thinning and decreased fractional shortening during >5 years o
f follow-up.
Conclusions-The Lys 183 del mutation in the cTnI gene in patients with HCM
is associated with variable clinical features and outcomes. HCM caused by t
he Lys 183 del mutation has a significant disease penetrance. This mutation
is associated with sudden death at any age and dilated cardiomyopathy-like
features in those aged >40 years. However, it remains unclear whether scre
ening of families with HCM for this mutation will be useful in patient mana
gement and counseling.