Two novel mutations and a new STK11/LKB1 gene isoform in Peutz-Jeghers patients.
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disorder with variable expression and incomplete penetrance characterized by mucocutaneous pigmentation, predisposition to hamartomatous intestinal polyposis, and various other neoplasms. It occurs in approximately 1 in 8,300 to 29,000 live births. In nearly 50% of patients PJS is caused by germ line mutations in the STK11/LKB1 serine/threonine kinase gene, the only kinase gene currently known to act as a tumor suppressor. We have performed a mutation search in the STK11/LKB1 gene in 8 sporadic cases and 3 PJS families using a combination of different screening techniques. We have identified four mutations, two of which I177N and the IVS2+1A->G, were previously unreported. We have also evaluated the presence of cDNA alterations by means of RT-PCR analysis and direct cDNA sequencing and have found two aberrant transcripts in a single PJS case despite the lack of any apparent genomic alteration. Finally, we report the presence of a novel STK11/LKB1 cDNA isoform observed in all the normal subjects studied as well as in the majority of the PJS patients.
Sez. Genetica Medica DIMIMP, Università di Bari, Italy.
N
N
Resta
A
A
Stella
F C
FC
Susca
M
M
Di Giacomo
G
G
Forleo
I
I
Miccolis
F P
FP
Rossini
M
M
Genuardi
A
A
Piepoli
P
P
Grammatico
G
G
Guanti
D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D000818:Animals; D015139:Blotting, Southern; D019556:COS Cells; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010580:Peutz-Jeghers Syndrome / Q000235:genetics* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D018076:DNA, Complementary; D004247:DNA; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases