Identification of PTEN mutations in five families with Bannayan-Zonana syndrome

Germline mutations in PTEN, a putative tumor suppressor gene, has been iden tified in 2 autosomal dominant inherited hamartoma syndromes, Cowden syndro me (CS) and Bannayan-Zonana syndrome (BZS). While both diseases exhibit dis tinct phenotypic features, there seems to be a partial clinical overlap bet ween the 2 diseases. To date, 9 families with BZS have been screened for PT EN mutations, of which 5 were found to exhibit mutations in this gene. We r eport 5 novel germline mutations in the PTEN coding sequence from 5 unrelat ed families with the BZS phenotype. While all the mutations we identified a re novel in BZS, 1003C-->T (nonsense mutation) and 209+5G-->A (putative spl ice site mutation) have been previously reported in unrelated families with CS and Lhermitte-Duclos disease. Interestingly, 1 of the families has an i ndividual with BZS and 1 with CS phenotype, associated with a single PTEN m utation, 885insA. These data support the notion that CS and BZS may be with in the spectrum of the same primary disorder.