Array-based genotype-phenotype correlation in a case of supernumerary ring chromosome 12.

Supernumerary ring chromosomes (SRC) account for approximately 10% of prenatal marker chromosomes and 60% of these SRCs are associated with an abnormal phenotype of the patient carrying them. SRCs have, with few exceptions, not been characterized at the molecular genetic level. Here, we present the first case of a SRC 12 thoroughly investigated with tiling resolution array-based comparative genomic hybridization (array CGH); multicolor, centromere, subtelomeric and whole chromosome painting fluorescence in situ hybridization. In addition, to be able to correlate phenotypic manifestations with a possible pathogenetic outcome of the SRC 12, we retrospectively compared and reviewed all 14 cases of SRC 12 reported, including our present case. Our analyses revealed that the SRC comprised 25.53-46.40 Mb of chromosome 12, a region known to harbor 47 annotated genes of which nine were of putative pathogenetic relevance. Reviewing the previously described cases of SRC 12, we could not establish any specific recurrent features associated with this type of SRC. This most probably reflects heterogeneity in break-point distribution among the reported cases, resulting in differently sized ring chromosomes and hence varying phenotypic traits of the patients. Detailed genomic evaluation, by array CGH or similar techniques may thus be of importance to predict the clinical course in individual cases.

Large intercommunity difference in cardiovascular drug consumption: relation to mortality, risk factors and socioeconomic differences.

A comparison of cardiovascular drug sales and cardiovascular mortality was made between two Swedish counties (Värmland and Malmöhus) and between two rural municipalities in those counties (Torsby in Värmland and Hörby in Malmöhus). Cardiovascular drug sales (defined daily doses (DDD) per 1,000 inhabitants per day) during 1986-87 were 25% higher in Värmland than in Malmöhus county, and the age-standardized mortality of coronary heart disease (CHD) was 36% (men) and 54% (women) higher. In Torsby, age-standardized CHD mortality (1986-87) was 71% (both sexes) higher than in Hörby, and the sales of cardiovascular drugs (1978-87) were 58% higher. Statistically, every third inhabitant of Torsby took one DDD of a cardiovascular drug every day, as compared to every fifth inhabitant in Hörby. In Torsby there was a 6% higher serum cholesterol, 71% lower tap water hardness, 33% lower income, a lower educational level, a three-fold higher unemployment rate, and a different ethnic background (20% eastern Finnish ancestry), all factors assumed to promote a high CHD rate. All of these factors may contribute to the higher CHD mortality, which was in turn reflected in higher sales of cardiovascular drugs.