BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a disease of the heart muscle, with an autosomal dominant mode of inheritance. It is also known as the 'disease of the sarcomere', and is a major cause of morbidity and mortality worldwide. Mutations in the sarcomeric genes have been largely implicated in the manifestation of HCM. Modifier genes and environmental factors, along with causative mutation, add to the cumulative effect of the disease. METHODS: In the present study, the role of the cardiac actin gene and the cardiac muscle LIM protein as contributors to HCM - through genetic variation - has been elucidated by screening the entire coding region in 100 control and 100 HCM subjects through polymerase chain reaction-based single-strand conformation polymorphism analysis and direct sequencing. RESULTS: The authors could not find any novel or reported exonic variations in any of the genes in the studied population; however, intronic variations were revealed in the cardiac actin gene through direct sequencing. A case of compound heterozygosity was observed in a patient with a variation in intron 1, along with a novel heterozygous mutation in exon 7 (S215L) of α-tropomyosin. CONCLUSIONS: The particular genes are highly conserved, and account for only 1.5% of HCM cases. They do not seem to play a major role in the genesis of HCM in the present population, thus confirming earlier reports of conserved sequences and ethnicity.
BACKGROUND:Hypertrophic cardiomyopathy (HCM) is a disease of the heart muscle, with an autosomal dominant mode of inheritance. It is also known as the 'disease of the sarcomere', and is a major cause of morbidity and mortality worldwide. Mutations in the sarcomeric genes have been largely implicated in the manifestation of HCM. Modifier genes and environmental factors, along with causative mutation, add to the cumulative effect of the disease. METHODS: In the present study, the role of the cardiac actin gene and the cardiac muscle LIM protein as contributors to HCM - through genetic variation - has been elucidated by screening the entire coding region in 100 control and 100 HCM subjects through polymerase chain reaction-based single-strand conformation polymorphism analysis and direct sequencing. RESULTS: The authors could not find any novel or reported exonic variations in any of the genes in the studied population; however, intronic variations were revealed in the cardiac actin gene through direct sequencing. A case of compound heterozygosity was observed in a patient with a variation in intron 1, along with a novel heterozygous mutation in exon 7 (S215L) of α-tropomyosin. CONCLUSIONS: The particular genes are highly conserved, and account for only 1.5% of HCM cases. They do not seem to play a major role in the genesis of HCM in the present population, thus confirming earlier reports of conserved sequences and ethnicity.
Authors: J Mogensen; A Perrot; P S Andersen; O Havndrup; I C Klausen; M Christiansen; P Bross; H Egeblad; H Bundgaard; K J Osterziel; G Haltern; H Lapp; P Reinecke; N Gregersen; A D Børglum Journal: J Med Genet Date: 2004-01 Impact factor: 6.318
Authors: E Takai; H Akita; N Shiga; K Kanazawa; S Yamada; M Terashima; Y Matsuda; C Iwai; K Kawai; Y Yokota; M Yokoyama Journal: Am J Med Genet Date: 1999-10-08
Authors: Satu Kärkkäinen; Keijo Peuhkurinen; Pertti Jääskeläinen; Raija Miettinen; Päivi Kärkkäinen; Johanna Kuusisto; Markku Laakso Journal: Am Heart J Date: 2002-06 Impact factor: 4.749