Genetic and clinical characteristics of Korean patients with neurofibromatosis type 2

Abstract

JGM approximately 1:40,000 to 60,000 [1,2]. NF2 is caused by a mutation in the NF2 gene located at chromosome 22 (22q12.2) and is inherited in an autosomal dominant manner. Approximately 50% of patients have no family history and approximately 25% to 30% of patients show somatic mosaicism [3,4]. Mutations are found in tumor tissues but are often not detectable in lym- IntroductionNeurofibromatosis type 2 (NF2, OMIM #101000) is characterized by vestibular schwannoma and other multiple tumors affecting cranial and peripheral nerves. Compared to the NF1 incidence of 1:3,000 to 5,000, the NF2 shows a lower incidence of www.e-kjgm.org Purpose: Neurofibromatosis type 2 (NF2) is characterized by multiple tumors, including vestibular schwannoma (VS) and others affecting cranial and peripheral nerves. NF2 is caused by mutation of the NF2 gene. The mutation spectrum of NF2 has not been characterized in Korean patients. In the current study, the clinical and genetic characteristics of Korean NF2 patients were analyzed. Materials and Methods: Twenty-five unrelated Korean families were enrolled according to the Manchester criteria. Genetic analysis was performed by direct sequencing and multiplex ligation-dependent probe amplification methods using genomic DNA from peripheral lymphocytes or tumor tissues. Results: All patients had bilateral/unilateral VS and/or other cranial and peripheral nerve tumors. Two patients were familial cases and the other 24 patients were sporadic. Germline NF2 mutations were detected in peripheral lymphocytes from both familial cases, but only in 26.1% of the 23 sporadic families. Somatic mutations were also found in tumor tissues from two of the sporadic families. These somatic mutations were not found in peripheral lymphocytes. A total of 10 different mutations including 2 novel mutations were found in 40.0% of studied families. Five mutations (50.0%) were located in exon 6 of NF2, the FERM domain coding region. Conclusion: Family history was an important factor in identifying germline NF2 mutations. Further study is required to investigate whether exon 6 is a mutation hotspot in Korean NF2 patients and its correlation to phenotypic severity.

Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma (BHP RCC)

“…The in-frame deletion occurs in a highly conserved C-terminal region of the merlin protein and includes the functionally significant serine-518 residue, the phosphorylation of which modulates merlin's ability to form intramolecular association between residues in the N-terminal and C-terminal domains 17 . The splice acceptor variant (c.600-1G>A) is likely pathogenic having been previously reported as a germline mutation in a young patient with bilateral vestibular schwannomas and meningioma 18 . Most of the NF2 variants were confirmed as somatically acquired (cases 1, 3, 4, 6-8).…”