Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis.
J Med Genet
; 45(6): 332-9, 2008 Jun.
Article
en En
| MEDLINE
| ID: mdl-18285426
ABSTRACT
BACKGROUND:
Schwannomatosis is a rare condition characterised by multiple schwannomas and lack of involvement of the vestibular nerve. A recent report identified bi-allelic mutations in the SMARCB1/INI1 gene in a single family with schwannomatosis. We aimed to establish the contribution of the SMARCB1 and the NF2 genes to sporadic and familial schwannomatosis in our cohort.METHODS:
We performed DNA sequence and dosage analysis of SMARCB1 and NF2 in 28 sporadic cases and 15 families with schwannomatosis.RESULTS:
We identified germline mutations in SMARCB1 in 5 of 15 (33.3%) families with schwannomatosis and 2 of 28 (7.1%) individuals with sporadic schwannomatosis. In all individuals with a germline mutation in SMARCB1 in whom tumour tissue was available, we detected a second hit with loss of SMARCB1. In addition, in all affected individuals with SMARCB1 mutations and available tumour tissue, we detected bi-allelic somatic inactivation of the NF2 gene. SMARCB1 mutations were associated with a higher number of spinal tumours in patients with a positive family history (p = 0.004).CONCLUSION:
In contrast to the recent report where no NF2 mutations were identified in a schwannomatosis family with SMARCB1 mutations, in our cohort, a four hit model with mutations in both SMARCB1 and NF2 define a subset of patients with schwannomatosis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas Cromosómicas no Histona
/
Neurofibromina 2
/
Proteínas de Unión al ADN
/
Neurilemoma
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Med Genet
Año:
2008
Tipo del documento:
Article
País de afiliación:
Reino Unido