Molecular characterization of the NF2 gene in Korean patients with neurofibromatosis type 2: a report of four novel mutations.
BACKGROUND
Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by the NF2 tumor suppressor gene. However, the NF2 mutation characteristics in Korean patients are not sufficiently understood. In this study, we conducted a comprehensive mutational analysis in 7 Korean NF2 patients by performing direct sequencing and gene-dosage assessment.


METHODS
We analyzed all exons and flanking regions of NF2 by direct sequencing and screened the deletions or duplications involving NF2 by multiplex ligation-dependent probe amplification.


RESULTS
Four novel NF2 mutations, including 2 splice-site mutations (c.364-1G>A and c.886-3C>G), 1 frameshift mutation (c.524delA), and 1 missense mutation (c.397T>C; p.Cys133Arg), were identified in our patients. No large deletion or duplication was identified in our series. Subsequently, we identified an abnormal splicing product by using reverse transcription-PCR and direct sequencing in 2 patients with a novel splice-site mutation. The missense mutation c.397T>C was predicted to have harmful effects on protein function.


CONCLUSIONS
The detection rate of NF2 mutations in Korean patients (57%) is similar to those in other populations. Our results provided a greater insight into the mutational spectrum of the NF2 gene in Korean subjects.
Seong
Moon Woo
MW
Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
Yeo
Im Kyung
IK
Cho
Sung Im
SI
Park
Chul Kee
CK
Kim
Seung Ki
SK
Paek
Sun Ha
SH
Kim
Dong Gyu
DG
Jung
Hee Won
HW
Park
Hyunwoong
H
Kim
So Yeon
SY
Kim
Ji Yeon
JY
Park
Sung Sup
SS
D024509:3' Flanking Region / Q000235:genetics; D024506:5' Flanking Region / Q000235:genetics; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D016518:Neurofibromatosis 2 / Q000175:diagnosis / Q000235:genetics*; D022821:RNA Splice Sites; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D055815:Young Adult
D022821:RNA Splice Sites