Whole exome sequencing reveals that the majority of schwannomatosis cases remain unexplained after excluding SMARCB1 and LZTR1 germline variants
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Schwannomatosis (MIM #162091) is characterized by the development of multiple schwannomas without vestibular nerve involvement (which is a characteristic of neurofibromatosis type 2—NF2—MIM #101000). About 10 % of patients have a family history of the disease, with the remaining 90 % presumed to be sporadic . Germline mutations of NF2 are not observed , although schwannomas frequently harbor somatic NF2 mutations and often display chromosome 22 loss . Rare cases with somatic mosaicism for NF2 alterations have also been described . Germline mutations in SMARCB1 (INI1), located proximal to NF2 on chromosome 22, are found in ~30–60 % of familial and ~10 % of sporadic schwannomatosis patients [4, 10, 12]. Recently, another schwannomatosis-predisposing gene within the 22q candidate region has been identified. Piotrowski et al.  reported germline loss-of-function mutations in LZTR1 in 80 % of familial and sporadic schwannomatosis cases with combined chr22 loss and somatic NF2...
KeywordsCOQ6 Copy Number Alteration Whole Exome Sequencing Somatic Mosaicism Copy Number Profile
For technical support and expertise we thank the High Throughput Sequencing and Microarray Units of the DKFZ Genomics and Proteomics Core Facility. This work was principally supported by the PedBrain Tumor Project contributing to the International Cancer Genome Consortium, funded by German Cancer Aid (DKH, #109252) and by the German Federal Ministry of Education and Research (BMBF, #01KU1201A, MedSys #0315416C and NGFNplus #01GS0883). Additional support came from the German Cancer Research Center—Heidelberg Center for Personalized Oncology (DKFZ-HIPO).