We have analyzed 61 German @entity0 families for @entity5345 mutations using single-strand conformation polymorphism analysis (SSCP) followed by sequencing. Forty-seven of the families had at least three cases (at least two under 60 years) and 14 families had only two cases of @entity5344 (at least one under 50 years). Twenty-eight families were @entity5344 were @entity0 families. Eighteen mutations in @entity5345 were detected in 11/28 @entity5344 families and 7/33 @entity0 families and none in the families with only two cases. We identified 17 truncation mutations (8 frameshift, 7 nonsense and 2 splice variants) and one missense mutation. Seven of these are novel and two, the @entity26207 and @entity70489 mutations, occurred in two apparently unrelated families. The genotype of the two families with the @entity26207 mutation is compatible with the rare haplotype segregating with the @entity26207 mutation in different populations, further supporting its European origin. One unclassified missense alteration, @entity70490 , was found in one family but did not segregate with the disease, suggesting that it is more likely a polymorphism. We also report and discuss the sequence of several new unclassified single- @entity377 changes first identified by SSCP. Of the 18 mutations, 13 occurred in the 3' third of the gene (end of exon 11-24) and @entity43 were found in eight of these families.

A high proportion of mutations in the @entity5345 gene in German XXXX families with clustering of mutations in the 3' third of the gene.

@entity26207 :: ('c|INS|5382|C', 'DNAMutation') :: ['5382insC'] @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian cancers'] @entity70489 :: ('c|SUB|C|5622|T', 'DNAMutation') :: ['5622C-->T'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast and breast/ovarian cancer', 'breast cancer', 'breast cancer-only'] @entity5344 :: ('MESH:D061325', 'Disease') :: ['breast/ovarian cancer', 'breast/ovarian and 33'] @entity5345 :: ('672', 'Gene') :: ['BRCA1'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity70490 :: ('p|SUB|R|841|W', 'ProteinMutation') :: ['R841W']
@entity5344 :: (MESH:D061325,Disease) :: ['breast/ovarian cancer']
