한국인 제2형 신경섬유종증 환자의 유전학적 및 임상적 특성
Genetic and clinical characteristics of Korean patients with neurofibromatosis type 2
Abstract
Introduction: Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by multiple tumors on nerve tissue. It usually involves the uni- or bilateral vestibular schwannoma (VS), as well as other tumors affecting cranial and peripheral nerves. NF2 is caused by mutation of the NF2 gene. The mutation spectrum of NF2 in Korean patients has not been known. Here we described the clinical and genetic characteristics of Korean NF2 patients. Methods: Twenty-six patients from 25 unrelated Korean families were enrolled according to the Manchester criteria. Genetic testing was performed by direct PCR sequencing and multiplex ligation-dependent probe amplification (MLPA) methods using genomic DNA from peripheral lymphocytes or tumor tissues. Results: All patients had bilateral/unilateral VS and/or other multiple tumors affecting cranial and peripheral nerves. About 50% of patients complained of severe hearing disturbance at the time of diagnosis. Two patients were diagnosed due to incidentally-found neurogenic tumors without symptoms. Two patients were familial cases and the other 24 patients were sporadic. Germline NF2 mutations were detected in peripheral lymphocytes from both familial cases, whereas only in 6 of the 23 families without family history (26%). Somatic NF2 mutations not found in peripheral lymphocytes were found in the tumor tissues from the two sporadic families. A total of 10 different mutations including 2 novel mutations were found in 40% of studied families. Five mutations (50%) were located in exon 6 of NF2, the FERM domain coding region. Conclusions: Family history was important factor in detecting germline NF2 mutations. Further study is needed to investigate whether exon 6 is a mutation hotspot in Korean NF2 patients and its correlation to severity of the phenotype.