Familial occurrence of schwannomas and malignant rhabdoid tumour associated with a duplication in SMARCB1.
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.


CONCLUSIONS
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.
Swensen
J J
JJ
ARUP Laboratories, and Department of Pathology, University of Utah, Salt Lake City, Utah 84108, USA. jeffrey.swensen@aruplab.com
Keyser
J
J
Coffin
C M
CM
Biegel
J A
JA
Viskochil
D H
DH
Williams
M S
MS
D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005190:Family; D020440:Gene Duplication; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008969:Molecular Sequence Data; D009442:Neurilemmoma / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D018335:Rhabdoid Tumor / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors