Background: The type II form of neurofibromatosis (NF2) is an autosomal dominant multiple neoplasia syndrome characterized by tumors of the eighth cranial nerve (usually bilateral), meningiomas of the brain, and schwannomas of the dorsal roots of the spinal cord. The incidence of neurofibromatosistype II is 1 in 25,000 live births.
Methods: To further understand the genetic spectrum of NF2, we analyzed an individual affected with multifocal schwanomatosis by whole exome sequencing. Potential candidate mutations were checked in additional familymembersto determine if the putative mutation segregated with disease status.
Results: No pathogenic variant was identified in NF1 and NF2 genes however, a novel nonsense homozygous mutation p.Q675X in PMS1 gene was identified. Direct sequencing confirmed that the patient is homozygous and her parents are heterozygous for the identified variant.
Conclusions: To the best of our knowledge it is the first report of involvement of PMS1 mutations in NF2. However, genetic testing of NF1 and NF2 genes in affected tissues to rule out somatic mutations as well as functional study for the identified variant are required to clarify under what circumstances mutations of this gene cause tumorigenesis.