To investigate gene mutation and clinical features in families with hereditary neurofibromatosis type 2 (NF2).

From January 2011 to December 2014, 37 patients with NF2 from 15 pedigrees treated in Beijing Tiantan Hospital, Capital Medical University were enrolled retrospectively. Thirty-one blood samples and 15 tumor samples (1 case from each pedigree) from patients were obtained; meanwhile, 74 blood samples from healthy controls (24 samples from healthy persons in the pedigrees and 50 samples from healthy persons without kinship) were obtained. Sanger sequencing method was used to sequence the NF2 gene coding region and its adjacent introns. Kaplan-Meier survival curve analysis was used to compare the different types of mutations and the survival period of the patients with different mutations.

Fifteen and 18 NF2 gene mutation types were detected from blood and tumor samples in patients with NF2, including 2 nonsense mutations, 4 missense mutations, 6 frameshift mutations, 1 in-frame deletion mutation, and 5 splice site mutations, 14 of the mutation types had not been reported. No NF2 gene mutations were detected in all the healthy subjects. Kaplan-Meier survival curves showed that the median survival time of the 18 patients in the NF2 gene nonsense/frameshift mutation group was 120.0±20.3 months; that of 11 patients in the missense mutation group was 288.0±91.7 months; and that of mutation site located in the NF2 gene 1-7 exon group of the 14 patients was 120.0±15.3 months; and that of mutation site located in the NF2 gene 8-11 exon group of the 15 patients was 276.0±19.6 months. There were significant differences (P=0.01, P=0.005).

NF2 gene mutation detection is an important method of early diagnosis and screening. The mutation style and sites are the important bases for identifying NF2 disease progression and prognosis.

Neurofibromatosis Type 2; Gene mutation; Heredity; Gene sequencing; Diagnosis