Individualized diagnosis and treatment of neurofibromatosis type II guided by molecular genetic analysis

Abstract

Objective To establish a molecular genetic analysis method applicable clinically for genetic diagnosis of patients with neurofibromatosis type Ⅱ (NF2) and their offsprings, and further guide the genetic counseling of NF2 family, condition monitoring, follow-up as well as clinical intervention of the patients. Methods Ten patients with NF2, admitted to our hospital from January 2009 to January 2010, were chosen;tumorigenic Schwann cells in Schwannoma were isolated and purified for primary culture. Genomic DNA was extracted from tumorigenic Schwann cells and from the blood of 2 patients and their offsprings who agreed to accept gene sequencing;the NF2 gene was sequenced (El-15 and El7 exons and adjacent introns). According to the implication of NF2 gene sequencing, genetic counseling was given to the NF2 family, and the potential NF2 patients in offsprings were followed up in a long-term. Results Schwannoma tissue and genomic DNA bank were established initially. Totallysame NF2 gene mutations were detected in genomic DNA extracted both from tumorigenic Schwann cells and blood cells in the same patient. By comparing the genotypes between the patients and the offsprings,consistent NF2 gene mutations were found between a female patient and her daughter aged 3, but not completely consistent gene mutations between another female patient and her son aged 15. All of the mutations in NF2 gene were located in the control region near the exons. Based on the patient's clinical manifestations and symptoms, reasonable plans for clinical interventions and follow-up were developed.Conclusion Schwannoma tissue and genomic DNA bank could supply the bio-resource for genetic molecular testing and treatment studies. Molecular genetic analysis would apply in clinical practice guidance, NF2 risk prediction, and follow-up plan for high-risk NF2 individuals. Early diagnosis and treatment, condition monitoring and long term follow-up and personalized clinical intervention are needed to improve the quality of life and prolong the survival. Key words: Neurofibromatosis type Ⅱ; Molecular genetic analysis; Clinical intervention