A HETEROZYGOUS FRAMESHIFT MUTATION OF THE PTEN MMAC1 GENE IN A PATIENT WITH LHERMITTE-DUCLOS-DISEASE - ONLY THE MUTATED ALLELE WAS EXPRESSED IN THE CEREBELLAR TUMOR/

Lhermitte-Duclos disease is a rare disorder of the cerebellum which ex hibits a focally indolent growth of the cerebellar cortex. The disease is sometimes associated with multiple hamartoma syndrome, or Cowden d isease, an autosomal, dominantly inherited cancer syndrome. Germline m utations of the PTEN/MMAC1 gene, a gene recently discovered to be a tu mor suppressor, have been documented in four families with Cowden dise ase. A family member in one of these families have had Lhermitte-Duclo s disease, indicating that mutations of the gene are responsible for t he development of Lhermitte-Duclos disease. However, the occurrence of Lhermitte-Duclos disease is mostly sporadic. It is unknown whether th e PTEN/MMAC1 gene is involved in these cases. We performed a genetic a nalysis on a patient with Lhermitte-Duclos disease, as well as analyse s on his family members, and found a germline mutation of the PTEN/MMA C1 gene. An insertion of A at nucleotide 83 in codon 28 was apparent i n both the patient and members of his family. This mutation caused a f rame shift that generated a premature stop codon in codon 43. The muta tion was heterozygous, although only the mutated allele was expressed in the cerebellar tumor of the patient. A monoallelic expression of th e mutated PTEN/MMAC1 gene may have been responsible for the developmen t of a cerebellar tumor in the patient.