Targeted massively parallel sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas: An analysis of 51 individuals in a single-center experience
| العنوان: | Targeted massively parallel sequencing of candidate regions on chromosome 22q predisposing to multiple schwannomas: An analysis of 51 individuals in a single-center experience |
|---|---|
| المؤلفون: | Piotrowski, A, Koczkowska, M, Poplawski, AB, Bartoszewski, R, Kroliczewski, J, Mieczkowska, A, Gomes, A, Crowley, MR, Crossman, DK, Chen, YJ, Lao, P, Serra, E, Llach, MC, Castellanos, E, Messiaen, LM |
| المصدر: | Human Mutation r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname |
| بيانات النشر: | John Wiley & Sons Inc., 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | low level mosaicism, schwannomatosis, deep intronic variant, NEFH, massively parallel sequencing, NF2, MYO18B, SMARCB1, LZTR1, SBF1, SGSM1, SGSM3 |
| الوصف: | Constitutional LZTR1 or SMARCB1 pathogenic variants (PVs) have been found in similar to 86% of familial and similar to 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. |
| تدمد: | 1059-7794 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=RECOLECTA___::8a2c9b69a94ea61b350083d9a05e7393 https://fundanet.igtp.cat/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1532 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.RECOLECTA.....8a2c9b69a94ea61b350083d9a05e7393 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10597794 |
|---|