Background Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors. Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. We analysed 14 cases of polymorphisms located in 10 candidate loci, in a sample of patients with T2D and controls from Mexico City.

The factor IX gene (F9) is an advantageous system for analyzing recent spontaneous germline mutation in humans. Herein, the male:female ratio of mutation ("r") in F9 have been estimated by Bayesian analysis from 59 germline origin families. The overall "r" in F9 was estimated at 3.75. The "r"s varied with the type of mutation. The "r"s ranged from 6.65 and 6.10 for transitions at CpG and A:T to G:C transitions at non-CpG dinucleotides, respectively, to 0.57 and 0.42 for microdeletions/microinsertions and large deletions (>1 kb), respectively. The "r" for the two subtypes of non-CpG transitions differed (6.10 for A:T to G:C vs 0.80 for G:C to A:T). Somatic mosaicism was detected in 11% of the 45 origin individuals for whom the causative mutation was visualized directly by genomic sequencing of leukocyte DNA (estimated sensitivity of approximately one part in 20). Four of the five defined somatic mosaics had G:C to A:T transitions at non-CpG dinucleotides, hinting that this mutation subtype may occur commonly early in embryogenesis. The age at conception was analyzed for 41 US Caucasian families in which the age of the origin parent and the year of conception for the first carrier/hemophiliac were available. No evidence for a paternal age effect was seen. However, an advanced maternal age effect was observed (P=0.03) and was particularly prominent for transversions (average of the 79th percentile when maternal age was normalized for the year of conception). This suggests that an increased maternal age results in a higher rate of transmitted mutation, whereas the increased number of mitotic replications associated with advanced paternal age has little, if any, effect on the rate of transmitted mutation.

In order to analyze the usefulness of different types of treatment in relation to the interval since the onset of idiopathic thrombocytopenic purpura (ITP), a collaborative study of 934 adult patients was undertaken. Prednisone was administered to 818 patients, and 32% of them achieved prolonged complete remission (PCR). However, only 14% of patients who had ITP for more than six months achieved a prednisone- induced PCR (P less than .01). Splenectomy was done in 399 patients, and 65% of them achieved PCR; the remission rate did not vary with the interval since the onset of ITP. Of 120 patients with chronic ITP that was refractory to corticosteroids and splenectomy, 91 received either azathioprine or cyclophosphamide; 21% of them achieved PCR and 55% had a favorable response. None of 19 patients treated with vincristine and only one of ten patients treated with vinblastine-loaded platelets achieved PCR.

SummaryGermline mutations in patients with hemophilia B generally have arisen within the past 150 years. Evidence suggests that these germline mutations generally result from endogenous processes. However, a unique pattern would be expected if a population were exposed to a physiologically important germline mutagen since mutagens generally produce characteristic patterns, or “fingerprints”, of mutation. To determine the pattern of mutation in Mexican Hispanics, the regions of likely functional significance in the factor IX gene were screened by di-deoxy fingerprinting (ddF) in 31 families with hemophilia B. Mutations were found in 30 of these families. Haplotype analysis was performed on individuals with identical mutations to help distinguish independent, recurrent mutations from founder effects. Analysis of these 30 mutations, along with 7 mutations reported previously in Mexican Hispanic families, reveals a pattern of independent mutation that is similar to the pattern of mutation observed in 127 U. S. Caucasian families (p = 0.89). These results may reflect either an underlying pattern of germline mutation due to endogenous processes or the presence of an ubiquitous mutagen. Further analyses of the recurrent mutations revealed that two mutations, T296M and R248Q, accounted for 19% of the mutations found in the Mexicans. Haplotype data suggest that the multiple occurrences of T296M and R248Q are associated with founder effects and that screening for these mutations may allow rapid mutation detection and carrier diagnosis in a significant minority of Mexican families with hemophilia B. These two mutations also are associated with founder effects in the U. S. Caucasian population. However, the haplotypes are different in these two populations, indicating independent origins. The occurrence of identical founder mutations in distinct populations provides evidence for the previous hypothesis that the number of different mutations giving rise to mild or borderline mild/moderate hemophilia B is small compared to deleterious mutations causing more severe disease.

SummaryA case with evidence of acquired von Willebrand’s syndrome associated with systemic lupus erythmatosus and Sjögren’s syndrome is described. The patient, who had no family history of bleeding, presented a haemorrhagic diathesis of recent origin, the bleeding time was prolonged, procoagulant Factor-VIII and von Willebrand factor levels were low and platelet aggregation was decreased with different concentrations of Ristocetin®.No improvement was seen after the tranfusion of cryoprecipitates, and there was no increase in procoagulant Factor-VIII.Clinical improvement resulted after treatment with corticosteroids, and later, the laboratory abnormalities characteristic of von Willebrand’s disease became normal. The level of procoagulant factor-VIII reached the very high level of 810%.