Novel Homozygous Nonsense Mutation of PMS۱ in a Patient with Multifocal Schwanomatosis Schwanomatosis Resembling Neurofibromatosis Type ۲

Background: The type II form of neurofibromatosis (NF۲) is an autosomal dominant multiple neoplasia syndrome characterizedby tumors of the eighth cranial nerve (usually bilateral), meningiomas of the brain, and schwannomas of the dorsal roots of thespinal cord. The incidence of neurofibromatosistype II is ۱ in ۲۵,۰۰۰ live births.Methods: To further understand the genetic spectrum of NF۲, we analyzed an individual affected with multifocal schwanomatosisbywholeexomesequencing. Potential candidate mutationswerechecked in additional familymembersto determine if the putativemutation segregated with disease status.Results: No pathogenic variant was identified in NF۱ and NF۲ genes however, a novel nonsense homozygous mutation p.Q۶۷۵X inPMS۱ gene was identified. Direct sequencing confirmed that the patient is homozygous and her parents are heterozygous for theidentified variant.Conclusions: To the best of our knowledge it is the first report of involvement of PMS۱ mutations in NF۲. However, genetic testing ofNF۱ and NF۲ genes in affected tissues to rule out somatic mutations as well as functional study for the identified variant are requiredto clarify under what circumstances mutations of this gene cause tumorigenesis.

کلیدواژه ها:

Neurofibromatosis Type ۲ ، PMS۱ ، Schwanomatosis