9 NOVEL GERMLINE MUTATIONS OF STK11 IN 10 FAMILIES WITH PEUTZ-JEGHERS-SYNDROME

Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary disea se characterized by hamartomatous polyposis involving the entire bowel . Recently STK11, a gene bearing a mutation responsible for PJS, was i solated. We investigated the entire coding region of STK11 in 15 unrel ated PJS families by the PCR-SSCP (polymerase chain reaction-single st rand conformation polymorphism) method and PCR-direct sequence analysi s, and found nine different, novel mutations among ten of those famili es. One nonsense mutation and five different frameshift mutations (two families carried the same mutation), all of which would cause truncat ion of the gene product, were found in seven families; mutations found in five families were clustered within exon 6. Among these five mutat ions, three occurred at the mononucleotide-repeat region (CCCCCC) of c odons 279-281, suggesting that this region is likely to be a mutationa l hotspot of this gene. One of the remaining three families carried a 3-bp in-frame deletion that would eliminate an asparagine residue with in a kinase domain of the product; the other two carried intronic muta tions at or adjacent to the consensus dinucleotide sequences of splice -acceptor or -donor sites, which were likely to lead to aberrant splic ing.