Establishment of EHMT1 mutant induced pluripotent stem cell (iPSC) line from a 11-year-old Kleefstra syndrome (KS) patient with autism and normal intellectual performance

Eszter Varga; Csilla Nemes; Zsuzsanna Táncos; István Bock; Sára Berzsenyi; György Lévay; Viktor Román; Julianna Kobolák; András Dinnyés

doi:10.1016/j.scr.2016.09.031

Establishment of EHMT1 mutant induced pluripotent stem cell (iPSC) line from a 11-year-old Kleefstra syndrome (KS) patient with autism and normal intellectual performance

Stem Cell Res. 2016 Nov;17(3):531-533. doi: 10.1016/j.scr.2016.09.031. Epub 2016 Oct 2.

Authors

Eszter Varga¹, Csilla Nemes¹, Zsuzsanna Táncos¹, István Bock¹, Sára Berzsenyi², György Lévay², Viktor Román², Julianna Kobolák¹, András Dinnyés³

Affiliations

¹ BioTalentum Ltd., Gödöllő, Hungary.
² Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary.
³ BioTalentum Ltd., Gödöllő, Hungary; Molecular Animal Biotechnology Laboratory, Szent István University, Gödöllő, Hungary. Electronic address: [email protected].

PMID: 27789404
DOI: 10.1016/j.scr.2016.09.031

Abstract

Peripheral blood was collected from a clinically characterized female Kleefstra syndrome patient with a heterozygous, de novo, premature termination codon (PTC) mutation (NM_024757.4(EHMT1):c.3413G>A; p.Trp1138Ter). Peripheral blood mononuclear cells (PBMCs) were reprogrammed with the human OSKM transcription factors using the Sendai-virus (SeV) delivery system. The pluripotency of transgene-free iPSC line was verified by the expression of pluripotency-associated markers and by in vitro spontaneous differentiation towards the 3 germ layers. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to study the pathomechanism of Kleefstra syndrome, also for drug testing, early biomarker discovery and gene therapy studies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autistic Disorder / complications
Autistic Disorder / genetics
Autistic Disorder / pathology*
Base Sequence
Cell Differentiation
Cell Line
Cellular Reprogramming
Child
Chromosome Deletion
Chromosomes, Human, Pair 9 / genetics
Craniofacial Abnormalities / complications
Craniofacial Abnormalities / genetics
Craniofacial Abnormalities / pathology*
Embryoid Bodies / cytology
Embryoid Bodies / metabolism
Female
Genetic Vectors / genetics
Genetic Vectors / metabolism
Heart Defects, Congenital / complications
Heart Defects, Congenital / genetics
Heart Defects, Congenital / pathology*
Histone-Lysine N-Methyltransferase / genetics*
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism
Intellectual Disability / complications
Intellectual Disability / genetics
Intellectual Disability / pathology*
Karyotype
Leukocytes, Mononuclear / cytology
Microscopy, Fluorescence
Polymorphism, Single Nucleotide
Sendai virus
Sequence Analysis, DNA
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

Transcription Factors
EHMT1 protein, human
Histone-Lysine N-Methyltransferase

Supplementary concepts

Kleefstra Syndrome