Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring
| Autor: | A Heiberg, R T Ramsden, A Moyhuddin, Andrew J Wallace, Michael E. Baser, D G R Evans, Shaun Purcell, C Watson |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Genetics
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty education.field_of_study Pediatrics Mutation Neuromuscular disease medicine.diagnostic_test business.industry Population medicine.disease medicine.disease_cause Germline otorhinolaryngologic diseases medicine Medical genetics Neurofibromatosis Age of onset business education Genetics (clinical) Genetic testing |
| Zdroj: | Journal of Medical Genetics. 40:459-463 |
| ISSN: | 1468-6244 |
| DOI: | 10.1136/jmg.40.6.459 |
| Popis: | Neurofibromatosis 2 (NF2), an autosomal dominant disorder that is characterised by tumours of cells of neural crest origin, is caused by inactivating mutations of the NF2 gene on chromosome 22q12.1,2 Bilateral vestibular schwannomas are the most frequent manifestation of the disease, but other central and peripheral nervous system schwannomas, cerebral meningiomas, and ocular abnormalities are also common.3–5 The birth incidence of NF2 is 1 in 33 000 to 1 in 40 000.6 Constitutional NF2 mutations have been found in 30-60% of NF2 patients, and genotype-phenotype correlations have been substantiated.7–12 Half of NF2 patients are new mutations,6 in whom constitutional NF2 mutations can occur either in parental germline cells (prezygotic) or in cells after fertilisation (postzygotic). Postzygotic mutations can result in mosaicism, defined as the presence of a mutation, deletion, or chromosomal abnormality in a group or population of cells.13 Owing to the rarity of NF2, most previous reports of mosaicism in NF2 have been limited in scope,14–16 although a recent study estimated that 25% of NF2 patients with new mutations are mosaic.17 In this study, we describe mutational analysis of 27 mosaic cases of NF2 and the results of genetic testing in their children. NF2 patients were identified through the United Kingdom NF2 registry in the Department of Medical Genetics, St Mary’s Hospital, Manchester. Patients are ascertained by contacting neurosurgeons, otolaryngologists, neurologists, paediatricians, dermatologists, and geneticists throughout the United Kingdom, augmented in the North West Region by the Regional Cancer Registry. There were 297 people from unrelated families who were screened for constitutional NF2 mutations; 256 had bilateral vestibular schwannomas and 41 met other Manchester clinical diagnostic criteria for NF2.3,18 Of these 297 families, 68 families had affected patients in more than one generation, but the … |
| Databáze: | OpenAIRE |
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