Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis 2
- T Tsilchorozidou1,
- F H Menko2,
- F Lalloo3,
- A Kidd7,
- R De Silva4,
- H Thomas4,
- P Smith3,
- A Malcolmson3,
- J Dore3,
- K Madan2,
- A Brown7,
- J G Yovos1,
- M Tsaligopoulos5,
- N Vogiatzis6,
- ME Baser,
- A J Wallace3,
- D G R Evans3
- 1Department of Endocrinology, Diabetes and Metabolism, AHEPA University Hospital, Thessaloniki, Greece
- 2Department of Clinical Genetics and Human Genetics, VU University Medical Center, Amsterdam, the Netherlands
- 3Academic Unit of Medical Genetics and Regional Genetics Service, St. Mary’s Hospital, Manchester, UK
- 4Department of Neurology, Oldchurch Hospital, Romford, Essex, UK
- 5Department of Otorhinolarygology and Hearing Impairment, AHEPA University Hospital, Thessaloniki, Greece
- 6Department of Paediatrics and Medical Genetics, AHEPA University Hospital, Thessaloniki, Greece
- 7Department of Medical Genetics, Wellington Hospital, Wellington, New Zealand
- Correspondence to: Professor D G R Evans Academic Unit of Medical Genetics and Regional Genetics Service, St. Mary’s Hospital, Manchester M13 0JH, UK; gareth.evanscmmc.nhs.uk
- Received 19 December 2003
- Accepted 19 December 2003
- CT, computed tomography
- MRI, magnetic resonance imaging
- NF2, neurofibromatosis type 2
- SSCP, single strand conformation polymorphism analysis
Neurofibromatosis type 2 (NF2) is an autosomal dominant condition characterised by vestibular schwannomas, schwannomas of other cranial nerves, meningiomas, and other low grade brain malignancies.1 The severity of NF2 is variable, with some patients having early onset disease and more rapidly growing tumours that occur in greater numbers. The NF2 gene is on chromosome 22q12.2,3 The protein product (termed merlin or schwannomin) is a cell cytoskeleton associating protein. Genotype−phenotype correlations have been demonstrated, with missense mutations and large deletions causing mild disease, and nonsense or frameshift mutations causing severe disease.4,5
The current mutation screening techniques of single strand conformation polymorphism analysis (SSCP), protein truncation test, and denaturing gradient gel electrophoresis detect 33–65% of mutations, although adding a deletion strategy increases the proportion to 80%.6 However, deletion testing and chromosome analysis are rarely reported in studies of NF2 mutations. In this study, we present five NF2 patients for whom chromosome analysis, usually following routine molecular screening, revealed the underlying genetic aberration.
CASE REPORTS
Case 1
A 20 year old female was referred with a large diffuse goitre commencing early in puberty, moderate learning difficulties, and bilateral sensorineural hearing loss, which resembles the phenotype of Pendred’s syndrome. She was born after a normal pregnancy and delivery. Her physical and mental development during early infancy was not remarkable, but developmental delay became apparent in the second year of life. Growth parameters were within the normal range. She began to walk at the age of 3 years. Six months later, audiometric tests showed no hearing impairment although chronic otitis media was diagnosed on one side. According to the parents, her communication had been improving with age, but her speech remained dysarthric and her articulation was very poor. In primary school, she had sub-average grades in all subjects. Her affect was good and …
