| Title: |
Somatic mosaicism in neurofibromatosis type 1 ; Соматический мозаицизм при нейрофиброматозе первого типа |
| Authors: |
K. O. Karandasheva; M. S. Pashchenko; N. A. Demina; I. A. Akimova; O. N. Makienko; M. S. Petuhova; L. A. Bessonova; I. V. Anisimova; A. S. Tanas; D. V. Zaletaev; V. V. Strelnikov; E. B. Kuznetsova; К. О. Карандашева; М. С. Пащенко; Н. А. Дёмина; И. А. Акимова; О. Н. Макиенко; М. С. Петухова; Л. А. Бессонова; И. В. Анисимова; А. С. Танас; Д. В. Залетаев; В. В. Стрельников; Е. Б. Кузнецова |
| Source: |
Medical Genetics; Том 18, № 5 (2019); 28-36 ; Медицинская генетика; Том 18, № 5 (2019); 28-36 ; 2073-7998 |
| Publisher Information: |
Publishing House «Genius Media» LLC |
| Publication Year: |
2019 |
| Collection: |
Medical Genetics (E-Journal) / Медицинская генетика |
| Subject Terms: |
NGS; NF1; соматический мозаицизм; высокопроизводительное параллельное секвенирование; neurofibromatosis; genetic mosaicism |
| Description: |
Background. Neurofibromatosis type 1 is one of the most common monogenic disorders. A pathogenic mutation in NF1 is the etiological factor of neurofibromatosis type 1. Nevertheless, not all patients receive molecular genetic verification of the clinical diagnosis. We believe that this may be due to a somatic mosaicism with a small fraction of pathogenic allele, which is neglected by the NGS analysis software and/or is undetectable by Sanger sequencing due to noisy background. Objective. To detect pathogenic mosaic mutations in cases of neurofibromatosis type 1 without germline genetic variants. Material and methods. Two hundred seventy five peripheral blood lymphocyte DNA samples from patients with NF1 and without germline mutation were retrospectively analyzed. DNA samples were sequenced with Ion PGM and Ion S5 NGS systems. Gene panel design included NF1 and NF2 genes: exons, adjacent intron segments (20-70 b.p.), 3’UTRs and 5’UTRs. Samples were also tested using MLPA in order to exclude deletions in NF1 and NF2. We developed and implemented the pipeline to search mosaic cases using bioinformatics approaches. All newly detected mutations were evaluated by Sanger sequencing and by heteroduplex analysis. Result. We have identified new pathogenic mutations in NF1 for 12 patients (4.4%) and verified 8 of them using alternative methods. Conclusion. Dominant disorders, like neurofibromatosis type 1, require a detailed bioinformatic analysis of NGS results with respect to somatic mosaicism. Our approach makes it possible to identify genetic variants with low representation of a pathogenic allele without increasing the sequencing depth of the sample under study and can be used for retrospective analysis of NGS data in order to improve the quality of DNA diagnostics. ; Актуальность. Нейрофиброматоз первого типа является одним из наиболее распространенных моногенных заболеваний. Этиологическим фактором его развития является патогенная мутация в гене NF1. Однако у части пациентов не удается достичь ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
Russian |
| Relation: |
https://www.medgen-journal.ru/jour/article/view/684/419 |
| DOI: |
10.25557/2073-7998.2019.05.28-36 |
| Availability: |
https://www.medgen-journal.ru/jour/article/view/684; https://doi.org/10.25557/2073-7998.2019.05.28-36 |
| Rights: |
Authors who publish with this journal agree to the following terms:Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access). ; Авторы, публикующие статьи в данном журнале, соглашаются на следующее:Авторы сохраняют за собой автороские права и предоставляют журналу право первой публикации работы, которая по истечении 6 месяцев после публикации автоматически лицензируется на условиях Creative Commons Attribution License , которая позволяет другим распространять данную работу с обязательным сохранением ссылок на авторов оригинальной работы и оригинальную публикацию в этом журнале.Авторы имеют право размещать их работу в сети Интернет (например в институтском хранилище или персональном сайте) до и во время процесса рассмотрения ее данным журналом, так как это может привести к продуктивному обсуждению и большему количеству ссылок на данную работу (См. The Effect of Open Access). |
| Accession Number: |
edsbas.2FF56F86 |
| Database: |
BASE |