Interpretation of Test Results

Interpretation of the results of exon-scanning tests requires identifying the underlying NF2 mutation at the genomic DNA or cDNA level, or both, to avoid false positives. Functional assays for merlin have been developed that can provide insight into the interpretation of missense and subtle in-frame alterations as pathogenic mutations rather than neutral polymorphisms;58-60 however, such assays may not be part of a clinical testing protocol. An international NF2 mutation database is available (Neurofibromatosis 2 Mutation Databases, http://uwcmml1s.uwcm.ac.uk/uwcm/ mg/nf2/), and this site also recognizes the United Kingdom population-based registry. Some mutations are also detailed in the Human Gene Mutation Data-base Cardiff (http://archive.uwcm.ac.uk/uwcm/mg/hgmd0.html). Somatic mosaicism or NF2 gene deletions must be considered in patients who have a negative mutation test using DNA from peripheral leukocytes, regardless of the severity of their manifestations. The risk of recurrence from mosaic parent to offspring is considered very low if an NF2 mutation cannot be identified in the parent.53 NF2 linkage tests should consider excluding the first affected member in a family; if they are mosaic, the linkage results will be misleading in the next generation.61 For similar reasons,linkage analysis for presymptomatic testing of subjects in this "next" generation should be performed with caution.

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