{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001005680"],"host":["EGA"],"description":["EGA study EGAS00001005680"],"dataset_title":["Targeted sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas"],"repository":["EGA"],"category":["restricted"],"additional_accession":[]},"is_claimable":false,"name":"Targeted sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas","description":"Constitutional LZTR1 or SMARCB1 pathogenic variants have been found in ~86% of familial and ~40% of sporadic schwannomatosis cases. Hence, we performed massively parallel sequencing of the entire LZTR1, SMARCB1 and NF2 genomic loci in 35 individuals with schwannomas negative for constitutional first-hit pathogenic variants in the LZTR1/SMARCB1/NF2 coding sequences, however with 22q deletion and/or a different NF2 pathogenic variant in each tumor, including six cases with only one tumor available. Furthermore, we verified whether any other LZTR1/SMARCB1/NF2 (likely) pathogenic variant(s) could be found in 16 cases carrying a SMARCB1 constitutional variant in the 3’ untranslated region (3’-UTR) c.*17C>T, c.*70C>T or c.*82C>T. As no additional variants were found, functional studies were performed to clarify the effect of these 3’-UTR variants on the transcript. The 3’-UTR variants c.*17C>T and c.*82C>T showed pathogenicity by negatively affecting SMARCB1 transcript level. Two novel deep intronic SMARCB1 variants, c.500+883T>G and c.500+887G>A, resulting in out-of-frame missplicing of intron 4, were identified in two unrelated individuals. Further resequencing of the entire repeat - masked genomics sequences of chromosome 22q in individuals negative for pathogenic variants in the SMARCB1/LZTR1/NF2 coding- and non-coding regions revealed five potential schwannomatosis-predisposing candidate genes, i.e. MYO18B, NEFH, SGSM1, SGSM3 and SBF1, pending further verification.","dates":{"updated":"2022-03-23 10:16:13"},"accession":"EGAS00001005680","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001008271","EGAC00001002363"]}}