👤 Juan Ramon Gimeno-Blanes

Hypertrophic cardiomyopathy (HCM) is characterized by an abnormal increase in myocardial mass that affects cardiac structure and function. HCM is the most common inherited cardiovascular disease in humans (0.2%) and the most common cardiovascular disease in cats (14.7%). Feline HCM phenotype is very similar to the phenotype found in humans, but the time frame for the development of the disease is significantly shorter. Similar therapeutic agents are used in its treatment and it has the same complications, such as heart failure, thromboembolism and sudden cardiac death. In contrast to humans, in whom thousands of genetic variants have been identified, genetic studies in cats have been limited to fragment analysis of two sarcomeric genes identifying two variants in MYBPC3 and one in MYH7. Two of these variants have also been associated with human disease. The high prevalence of the reported variants in non-affected cats hinders the assumption of their pathogenicity in heterozygotes. An in-depth review of the literature about genetic studies on feline HCM in comparison with the same disease in humans is presented here. The close similarity in the phenotype and genotype between cats and humans makes the cat an excellent model for the pathophysiological study of the disease and future therapeutic agents. Show less

Duchenne muscular dystrophy is a disorder with variable expression caused by framedisrupting mutations in the dystrophin gene. It is characterized by progressive muscle weakness and dilated cardiomyopathy. In-frame dystrophin mutations cause a clinically moderate disorder named Becker muscular dystrophy. Our aim was to study the clinical and genetic characteristics of a family with inherited cardiomyopathy and Becker muscular dystrophy. The index case was diagnosed with psychomotor retardation at 5 years of age. Asymmetric left ventricular hypertrophy and a long QT interval were evidenced at the age of 12. Mild muscular weakness was developed subsequently. Three genetic variants were identified in the index case: p.Arg891Alafs*160 in the MYBPC3 gene, p.Thr263Met in the KCNJ5 gene, and p.Ser2437_Ile2554delinsPhe in the DMD gene. The latter was expected to generate an in-frame deletion of exons 51 and 52 of the dystrophin gene. A family study revealed that the father and 3 uncles were carriers of the MYBPC3 mutation. The mother and a maternal grandfather were carriers of the other 2 variants. The 80-year-old grandfather, who had the dystrophin mutation, showed no sign of cardiomyopathy or muscular weakness. The deletion of exons 51 and 52 in the DMD gene, which has been proposed as one of the therapeutic strategies for Duchenne, is consistent with a normal life expectancy and the absence of myopathic symptoms in hemizygous males. Show less

Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous genetic heart disease characterized by left ventricular hypertrophy in the absence of another disease that could explain the wall thickening. Elucidation of the genetic basis of HCM lead to the identification of several genes encoding sarcomeric proteins, such as MYH7, MYBPC3, TPM1, TNNT2, and TNNI3. Sarcomeric genes are mutated in approximately 40% of HCM patients and a possible explanation for the incomplete yield of mutation-positive HCM may be somatic mutations. We studied 104 unrelated patients with non-familial HCM. Patients underwent clinical evaluation and mutation screening of 5 genes implicated in HCM (MYH7, MYBPC3, TPM1, TNNT2, and TNNI3) in genomic DNA isolated from resected cardiac tissue; 41 of 104 were found to carry a mutation, but as several patients carried the same mutations, the total amount of different mutations was 37; 20 of these mutations have been previously described, and pathogenicity has been assessed. To determine the effect of the 17 new mutations an in silico assay was performed and it predicted that 4 variants were damaging mutations. All identified variants were also seen in the DNA isolated from the corresponding blood, which demonstrated the absence of somatic mutations. Somatic mutations in MYH7, MYBPC3, TPM1, TNNT2, and TNNI3 do not represent an important etiologic pathway in HCM. Show less