title: Germline mutation of INI1/SMARCB1 in familial schwannomatosis.
abstract: Patients with schwannomatosis develop multiple schwannomas but no vestibular schwannomas diagnostic of neurofibromatosis type 2. We report an inactivating germline mutation in exon 1 of the tumor-suppressor gene INI1 in a father and daughter who both had schwannomatosis. Inactivation of the wild-type INI1 allele, by a second mutation in exon 5 or by clear loss, was found in two of four investigated schwannomas from these patients. All four schwannomas displayed complete loss of nuclear INI1 protein expression in part of the cells. Although the exact oncogenetic mechanism in these schwannomas remains to be elucidated, our findings suggest that INI1 is the predisposing gene in familial schwannomatosis.
authors.affiliation: Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. t.j.hulsebos@amc.uva.nl
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Hulsebos
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Plomp
authors.forename: Ruud A
authors.initials: RA
authors.lastname: Wolterman
authors.forename: Els C
authors.initials: EC
authors.lastname: Robanus-Maandag
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
mesh_terms: D000328:Adult; D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009442:Neurilemmoma / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors