title: Molecular analysis of the rhabdoid predisposition syndrome in a child: a novel germline hSNF5/INI1 mutation and absence of c-myc amplification.
abstract: The authors report a case of the rhabdoid predisposition syndrome (RPS) secondary to a germline hSNF5/INI1 mutation, whose brain tumor was originally unclassified but finally diagnosed as an atypical teratoid/rhabdoid tumor (AT/RT) by molecular analysis. A 7-month-old infant presented with hydrocephalus secondary to a huge pineal tumor and subsequently developed a renal rhabdoid tumor. The histology of the brain tumor was initially undetermined; however, an AT/RT was strongly suspected because of her clinical course. Mutational screening of the hSNF5/INI1 gene by heteroduplex and direct sequence analysis detected a missense mutation at codon 53 (CGA --> TGA, arginine --> stop) in both tumors, as well as in normal tissue of the kidney. Polymerase chain reaction (PCR)-based microsatellite analysis showed in both tumors allelic loss on chromosome arm 22q to which the hSNF5/INI1 gene maps. c-myc amplification was examined by differential PCR but not detected. Histologic review of the brain tumor by immunohistochemistry confirmed focal expression of epithelial membrane antigen and smooth muscle actin. These findings suggest that the brain tumor was really an AT/RT as a component of RPS secondary to a germline hSNF5/INI1 mutation. The present mutation has never been reported in the literature.
authors.affiliation: Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan. fujisawa@ns.m.kanazawa-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takabatake
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
authors.forename: Osamu
authors.initials: O
authors.lastname: Tachibana
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: Junkoh
authors.initials: J
authors.lastname: Yamashita
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D018335:Rhabdoid Tumor / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D000071796:SMARCB1 Protein; D013577:Syndrome; D014157:Transcription Factors
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors