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Open Access Highly Accessed Case report

Pathogenesis of vestibular schwannoma in ring chromosome 22

Ellen Denayer1, Hilde Brems1, Paul de Cock2, Gareth D Evans3, Frank Van Calenbergh4, Naomi Bowers3, Raf Sciot5, Maria Debiec-Rychter1, Joris V Vermeesch1, Jean-Pierre Fryns1 and Eric Legius1*

Author Affiliations

1 Department of human genetics, University Hospital Gasthuisberg, Leuven, Belgium

2 Department of Paediatrics, University Hospital Gasthuisberg, Leuven, Belgium

3 Genetic Medicine, Manchester Academic Health Science Centre, St Mary's hospital, Manchester, UK

4 Department of Neurosurgery, University Hospital Gasthuisberg, Leuven, Belgium

5 Department of Pathology, University Hospital Gasthuisberg, Leuven, Belgium

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BMC Medical Genetics 2009, 10:97  doi:10.1186/1471-2350-10-97

Published: 22 September 2009

Abstract

Background

Ring chromosome 22 is a rare human constitutional cytogenetic abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as different tumour types have been reported in patients with ring chromosome 22. The pathogenesis of these tumours is not always clear yet.

Methods

We report on a female patient with a ring chromosome 22 presenting with severe mental retardation, autistic behaviour, café-au-lait macules and facial dysmorphism. Peripheral blood lymphocytes were karyotyped and array CGH was performed on extracted DNA. At the age of 20 years she was diagnosed with a unilateral vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and NF2 mutation analysis.

Results

Karyotype on peripheral blood lymphocytes revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of the ring chromosome 22 and a somatic second hit in the NF2 gene on the remaining chromosome 22.

Conclusion

We conclude that tumours can arise by the combination of loss of the ring chromosome and a pathogenic NF2 mutation on the remaining chromosome 22 in patients with ring chromosome 22. Our findings indicate that patients with a ring 22 should be monitored for NF2-related tumours starting in adolescence.