Israel Medical Association Journal

Background: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.

Objectives: To analyze the impact of genetic diagnosis on the clinical management of HCM.

Methods: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.

Results: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.

Conclusions: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determine the indication for genetic testing and interpretation of the results.

Background: The Muslim Circassians in Israel represent a unique ethnic community, distinct from Jews and Arabs. This endogamous group has a limited genetic variability that allows studying risk factors associated with type 2 diabetes.

Objectives: To estimate the prevalence of type 2 diabetes among Israeli Circassians and its correlation to obesity and genetic susceptibility.

Methods: Israeli Circassian women (n=450) and men (n=289) older than 35 were included in the study. They were classified as having or not having diabetes, and their risk factors, including hypertension, body mass index, family history of diabetes, and laboratory tests, were examined retrospectively.

Results: The age-adjusted prevalence of diabetes among the 739 participants was 12% (men 14.6%, women 10.7%). It was higher among those with BMI[1] > 30 than in those with lower BMI and a family history of diabetes without high BMI. But the risk of diabetes with BMI > 30 plus a family history was three times higher than when these factors were missing (odds ratio 2.96, 95% confidence interval 1.30–6.6). Multivariate analysis, however, found familial history of diabetes to be the strongest risk factor, independent of obesity (OR[2] 2.47, 95% CI[3] 1.45–4.20).

Conclusions: The results yielded by this homogeneous Circassian population, sharing the same environmental influences and having an endogamous pattern of marriage, suggest a role of genetic risk factors for diabetes. Israeli Circassians are suitable for additional genetic studies that may lead to the identification of susceptibility genes for type 2 diabetes.