Background: The role of germline and somatic SMARCB1 gene mutations in malignant rhabdoid tumour (MRT) predisposition is well known. Germline SMARCB1 mutations have also recently been identified in a subset of individuals with schwannomatosis. Surprisingly, MRT predisposition and schwannomatosis have never been reported to co-occur in a family. The correlation between genotype and phenotype for mutations in SMARCB1 has not been determined.
Results: We have identified a germline 2631 bp duplication that includes exon 6 of SMARCB1 in a unique family with a four generation history of MRT predisposition and schwannomatosis. This duplication segregates with disease in individuals affected with both conditions, linking MRT predisposition and schwannomatosis as components of the same syndrome in this family.
Conclusion: The unique combination of tumours that result from the duplication described in this report may provide important clues about the mechanisms that influence the phenotype associated with a given SMARCB1 mutation.
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Funding: This work was supported in part by a grant from the NIH (CA46274) to JAB.
Competing interests: None.
Ethics approval: The University of Utah Clinical Genetics Research Program was approved by the University of Utah Institutional Review Board
Patient consent: Obtained.
CMC’s present affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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