Analysis of induced pluripotent stem cell clones derived from a patient with mosaic neurofibromatosis type 2

Abstract

The diagnosis of mosaicism is challenging in patients with neurofibromatosis type 2 (NF2) subset due to low variant allele frequency. In this study, we generated induced pluripotent stem cells (iPSCs) were generated from a patient clinically diagnosed with NF2 based on multiple schwannomas, including bilateral vestibular schwannomas and meningiomas. Genetic analysis of the patient's mononuclear cells (MNCs) from peripheral blood failed to detect NF2 alteration but successfully found p.Q65X (c.193C>T) mutation in all separate tumors with three intracranial meningiomas and one intraorbital schwannoma, and confirming mosaicism diagnosis in NF2 alteration using deep sequencing. Five different clones with patient-derived iPSCs

Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report

“…DNA extraction from frozen tumor tissue and mononuclear cells (MNC) in peripheral blood, PCR, and Sanger sequencing of IDH1/2 were performed as previously described 19,20 . The IDH1 R132H mutation was detected in MNC as well as right and left frontal lobe tumors (Fig.…”

MERLIN-DEFICIENT iPSCs AS ANIN VITROMODEL SYSTEM FOR STUDIYNGNF2PATHOGENESIS

“…The copyright holder for this preprint this version posted December 14, 2022. ; https://doi.org/10.1101/2022.12.14.520389 doi: bioRxiv preprint Induced pluripotent stem cell (iPSC) (33) models have been used in a wide range of diseases, representing an unlimited source of cells with diverse applications such as disease modelling, drug development, regenerative medicine or gene regulation (34)(35)(36)(37). The first related model reported for NF2-related SWN was an iPSC line harbouring a homozygous variant in the NF2 gene (UMi031-A-2), obtained through gene editing by CRISPR/Cas9 of a non-affected pluripotent cell line (38); and more recently, an iPSC clone has been derived from mononuclear bone marrow-derived stem cells of a mosaic NF2-related SWN patient (39). However, there is still the need to develop relevant disease models from these iPSC, which fully recapitulate the genetic and physiological status of NF2 derived VS.…”

“…Induced pluripotent stem cell (iPSC) (29) models have been used in a wide range of diseases and represent an unlimited source of cells with multiple applications such as disease modelling, drug development, regenerative medicine, or gene regulation (30)(31)(32)(33). The first NF2-related SWN model reported was an iPSC line harboring a homozygous variant in the NF2 gene (UMi031-A-2), obtained by CRISPR/Cas9 gene-editing of an unaffected pluripotent cell line (34); and, more recently, an iPSC clone was derived from mononuclear bone marrow stem cells from a mosaic NF2-related SWN patient (35).…”