The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations

BACKGROUND: Analysis of the chromosomal background upon which a mutation occurs can be used to reconstruct the origins of specific disease-causing mutations. The relatively common BRCA1 mutation, 1135insA, has been previously identified as a Norwegian founder mutation. We performed haplotype analysis of individuals from breast and ovarian cancer families from four different ethnic backgrounds who had been identified as carriers of the BRCA1: 1135insA mutation. METHODS: Four microsatellite markers (D17S855, D17S1322, D17S1323 and D17S1325) located within or near the BRCA1 gene were genotyped in mutation carriers from 6 families of French Canadian, Italian and Dutch descent. Haplotypes were inferred from the genotype data and compared between these families and with the previously reported Norwegian founder haplotype. RESULTS: The 1135insA mutation was found to occur on three distinct haplotype backgrounds. The families from Norway shared a distinct haplotype while the families of French Canadian, Italian, and Dutch descent were found to occur on one of two additional, distinct backgrounds. CONCLUSION: Our results indicate that while the Norwegian haplotype including 1135insA represents an ancient Norwegian mutation, the same mutation has occurred independently in the other populations examined. In centres where targeted mutation testing is performed, exclusively or prior to gene sequencing, our findings suggest that this recurring mutation should be included in targeted mutation panels, irrespective of the ethnic origin of the persons tested

Value of the case history in the diagnosis of allergic state and the detection of allergens

Detailed histories taken in eighty-one patients suffering from perennial asthma and rhinitis were analysed independently by three trained allergists and their conclusions were compared to the results of three tests: (1) concentration of total serum IgE; (2) skin tests and (3) radioallergosorbent test (RAST). In eleven patients (14%), the three investigators disagreed when estimating the allergic nature of the symptoms. Ten out of forty-four patients (23%), unanimously predicted not to be allergic, had high levels of total serum IgE and skin tests and RAST clearly positive for one or more allergens. The allergists suspected 47% of the allergens detected by skin tests and 55% of those detected by RAST. The case history was the test which most often gave information at odds with that suggested by the other three tests. Our study indicates therefore that a case history not even suggestive of allergy should be complemented by additional tests