title: 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.
abstract: Lhermitte-Duclos disease is a rare disorder of the cerebellum which exhibits a focally indolent growth of the cerebellar cortex. The disease is sometimes associated with multiple hamartoma syndrome, or Cowden disease, an autosomal, dominantly inherited cancer syndrome. Germline mutations of the PTEN/MMAC1 gene, a gene recently discovered to be a tumor suppressor, have been documented in four families with Cowden disease. A family member in one of these families have had Lhermitte-Duclos disease, indicating that mutations of the gene are responsible for the development of Lhermitte-Duclos disease. However, the occurrence of Lhermitte-Duclos disease is mostly sporadic. It is unknown whether the PTEN/MMAC1 gene is involved in these cases. We performed a genetic analysis on a patient with Lhermitte-Duclos disease, as well as analyses on his family members, and found a germline mutation of the PTEN/MMAC1 gene. An insertion of A at nucleotide 83 in codon 28 was apparent in both the patient and members of his family. This mutation caused a frame shift that generated a premature stop codon in codon 43. The mutation was heterozygous, although only the mutated allele was expressed in the cerebellar tumor of the patient. A monoallelic expression of the mutated PTEN/MMAC1 gene may have been responsible for the development of a cerebellar tumor in the patient.
authors.affiliation: Internal Medicine, Minami Wakayama National Hospital, Tanabe, Wakayama 646, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Iida
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Nagareda
authors.forename: K
authors.initials: K
authors.lastname: Moriwaki
mesh_terms: D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D016368:Frameshift Mutation; D005729:Ganglioneuroma / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins
chemical_list: D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human