Targeted massively parallel sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas: An analysis of 51 individuals in a single-center experience.

Autor: Piotrowski A; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.; 3P-Medicine Laboratory, Medical University of Gdansk, Gdansk, Poland.; Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland., Koczkowska M; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.; 3P-Medicine Laboratory, Medical University of Gdansk, Gdansk, Poland.; Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland., Poplawski AB; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA., Bartoszewski R; Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland., Króliczewski J; Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland., Mieczkowska A; Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland., Gomes A; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA., Crowley MR; Genomic Core Facility, University of Alabama at Birmingham, Birmingham, Alabama, USA., Crossman DK; Genomic Core Facility, University of Alabama at Birmingham, Birmingham, Alabama, USA., Chen Y; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA., Lao P; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA., Serra E; Hereditary Cancer Group, Program of Predictive and Personalized Medicine of Cancer (PMPPC), Germans Trias i Pujol Research Institute (IGTP), Barcelona, Spain., Llach MC; Hereditary Cancer Group, Program of Predictive and Personalized Medicine of Cancer (PMPPC), Germans Trias i Pujol Research Institute (IGTP), Barcelona, Spain., Castellanos E; Clinical Genomics Research Group, Program of Predictive and Personalized Medicine of Cancer (PMPPC), Germans Trias i Pujol Research Institute (IGTP), Barcelona, Spain.; Clinical Genomics Unit, Clinical Genetics Service, Northern Metropolitan Clinical Laboratory, Germans Trias i Pujol University Hospital (HUGTiP), Barcelona, Spain., Messiaen LM; Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2022 Jan; Vol. 43 (1), pp. 74-84. Date of Electronic Publication: 2021 Nov 15.
DOI: 10.1002/humu.24294
Abstrakt: Constitutional LZTR1 or SMARCB1 pathogenic variants (PVs) 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 PVs in the LZTR1/SMARCB1/NF2 coding sequences; however, with 22q deletion and/or a different NF2 PV in each tumor, including six cases with only one tumor available. Furthermore, we verified whether any other LZTR1/SMARCB1/NF2 (likely) PVs 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 the 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 PVs in the SMARCB1/LZTR1/NF2 coding- and noncoding regions revealed five potential schwannomatosis-predisposing candidate genes, that is, MYO18B, NEFH, SGSM1, SGSM3, and SBF1, pending further verification.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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