A BRCA1 founder mutation, identified with haplotype analysis, allowing genotype/phenotype determination and predictive testing

We searched for a founder mutation in a population from one geographic region of Norway with prevalent breast/ovarian cancer families. We sampled 33 breast/ovarian cancer families and determined haplotypes of four markers linked to the BRCA1 region. Of the affected 33 index women, 13 (39.4%) shared one haplotype. In five (15% of total), an identical mutation was indicated by an abnormal truncated protein test (PTT) of exon 11 and shown to represent a 1675delA mutation. In the other index women, PTT of exon 11 showed no abnormality. No other BRCA1 founder mutation of this prevalence is likely because no other haplotype was more frequent in affecteds than in controls. All families with the 1675delA mutation in this geographic region may be considered as part of one large kindred. This allows a genotype-phenotype correlation to be precisely determined and used in genetic counselling for predictive testing within this kindred. Identification of identical haplotypes between unrelated affected individuals may be used to estimate the extent of founder effects for any mapped disease, without knowledge of the specific founder mutation. (C) 1997 Elsevier Science Ltd

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BACKGROUND: Loss-of-function mutations in CHD7 cause Coloboma, Heart Disease, Atresia of Choanae, Retardation of Growth and/or Development, Genital Hypoplasia, and Ear Abnormalities With or Without Deafness (CHARGE) syndrome, a variable combination of multiple congenital malformations including heart defects. Heart defects are reported in 70% to 92% of patients with a CHD7 mutation, but most studies are small and do not provide a detailed classification of the defects. We present the first, detailed, descriptive study on the cardiac phenotype of 299 patients with a CHD7 mutation and discuss the role of CHD7 in cardiac development. METHODS AND RESULTS: We collected information on congenital heart defects in 299 patients with a pathogenic CHD7 mutation, of whom 220 (74%) had a congenital heart defect. Detailed information on the heart defects was available for 202 of these patients. We classified the heart defects based on embryonic cardiac development and compared the distribution to 1007 equally classified nonsyndromic heart defects of patients registered by EUROCAT, a European Registry of Congenital Anomalies. Heart defects are highly variable in patients with CHD7 mutations, but atrioventricular septal defects and conotruncal heart defects are over-represented. Sex did not have an effect on the presence of heart defects, but truncating CHD7 mutations resulted in a heart defect significantly more often than missense or splice-site mutations (chi(2), P<0.001). CONCLUSIONS: CHD7 plays an important role in cardiac development, given that we found a wide range of heart defects in 74% of a large cohort of patients with a CHD7 mutation. Conotruncal defects and atrioventricular septal defects are over-represented in patients with CHD7 mutations compared with patients with nonsyndromic heart defects

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Genetics of disease, diagnosis and treatmen

Thalassiosira species (Bacillariophyceae) from a Scottish sea-loch

During the spring diatom blooms of 1992 and 1993 in Loch Creran, Scotland, regular water column and sediment samples were collected, examined, and species composition of the phytoplankton determined. Thalassiosira species were found to be a major bloom constituent. Species were identified from specimens cultured from sediments and isolated from vertical net hauls, using light and scanning electron microscopy. Of the 17 species positively determined, only Thalassiosira angulata, T. anguste-lineata, T. eccentrica, T. gravida, T. minima, T. nordenskioeldii, T. rotula and T. tenera have been previously reported in Scottish waters. Other species, for example Thalassiosira pseudonana and T. punctigera, have been noted elsewhere in the British Isles but not along the Scottish west coast. Several species, namely Thalassiosira concaviuscula, T. constricta, T. delicatula, T. kuschirensis, T. oceanica, T. pacifica and T. tealata, are new records for the British Isles. One unidentified taxon is illustrated. Descriptions, illustrations and a key are provided for the 18 taxa