SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis.
BACKGROUND
Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic NF2 mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the SMARCB1 (INI1) tumor suppressor gene were described in familial and sporadic schwannomatosis patients.


METHODS
To delineate the SMARCB1 gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas.


RESULTS
Nine variants scattered along the sequence of SMARCB1 were identified. Five of them were classified as deleterious. All five patients carrying a SMARCB1 mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age.


CONCLUSIONS
These results suggest that patients with schwannomas have a significant probability of carrying a SMARCB1 mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the SMARCB1 gene.
Laboratory of Molecular Oncogenetics, Institut Paoli-Calmettes, Marseille, France.
Guillaume
G
Rousseau
Tetsuro
T
Noguchi
Violaine
V
Bourdon
Hagay
H
Sobol
Sylviane
S
Olschwang
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000235:genetics; D017253:Neurofibromatoses / Q000235:genetics; D000071796:SMARCB1 Protein; D017422:Sequence Analysis, DNA / Q000379:methods; D012878:Skin Neoplasms / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors
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