Molecular Identification of the Schwannomatosis Locus.

摘要

In 2007, mutations in the SMARCB1 tumor suppressor (also known as INI1 and hSNF5), which lies in the familial schwannomatosis candidate region, were detected on a somatic and constitutional level in a single kindred with schwannomatosis. We have completed our study of 19 schwannomatosis kindreds who were unrelated to the best of the study participants' knowledge. Overall, we identified potentially causative constitutional alterations in 13 families, including 2 missense mutations (in 3 families), 4 splice site mutations, 2 additional mutations thought to be splice site mutations, and 4 changes of presumed pathogenicity in exon 9 (c.1240C>T). We compared haplotypes of the retained (affected) allele in tumors from families with recurrent mutations in SMARCB1. Differing haplotypes were seen in 4 families with the c.1240C>T mutation in exon 9, which argues against a common ancestor. In contrast, a similar haplotype was seen in 2 families for c.158G>T mutation in exon 2 which suggests a common ancestor.