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.

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