SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis

Guillaume Rousseau,Sylviane Olschwang,Violaine Bourdon,Tetsuro Noguchi,Hagay Sobol

doi:10.1186/1471-2377-11-9

Abstract

BackgroundSchwannomatosis 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.MethodsTo 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.ResultsNine 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.ConclusionsThese 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.

Highlights

Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas
Patients with multiple nonvestibular schwannomas have been assembled into a particular category within neurofibromatoses called schwannomatosis [1]
To improve the clinical indications for SMARCB1 molecular screening in medical genetics practice, we evaluated its implication in a series of patients exhibiting non-vestibular schwannomas and no NF2 germline alteration

Summary

Introduction

Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Germline mutations of the SMARCB1 (INI1) tumor suppressor gene were described in familial and sporadic schwannomatosis patients. Patients with multiple nonvestibular schwannomas have been assembled into a particular category within neurofibromatoses called schwannomatosis [1]. The SMARCB1 gene has been found to harbor germline alterations in both familial and sporadic schwannomatosis patients [2,3], with a greater number of spinal schwannomas in familial cases and the presence of meningiomas [4] this latter point remains debated [5]. To improve the clinical indications for SMARCB1 molecular screening in medical genetics practice, we evaluated its implication in a series of patients exhibiting non-vestibular schwannomas and no NF2 germline alteration

Methods

Results

Conclusion