Establishment and characterization of ZJUCHi003: an induced pluripotent stem cell line from a patient with Temple-Baraitser/Zimmermann-Laband syndrome carrying KCNH1 c.1070G > A (p.R357Q) variant

Hum Cell. 2024 May;37(3):832-839. doi: 10.1007/s13577-024-01031-8. Epub 2024 Feb 19.

Abstract

Pathogenic variants of the KCNH1 gene can cause dominant-inherited Temple-Baraitser/Zimmermann-Laband syndrome with severe mental retardation, seizure, gingival hyperplasia and nail hypoplasia. This study established an induced pluripotent stem cell (iPSC) line using urinary cells from a girl with KCNH1 recurrent/hotspot pathogenic variant c.1070G > A (p.R357Q). The cell identity, pluripotency, karyotypic integrity, absence of reprogramming virus and mycoplasma contamination, and differential potential to three germ layers of the iPSC line, named as ZJUCHi003, were characterized and confirmed. Furthermore, ZJUCHi003-derived neurons manifested slower action potential repolarization process and wider action potential half-width than the normal neurons. This cell line will be useful for investigating the pathogenic mechanisms of KCNH1 variants-associated symptoms, as well as for evaluating novel therapeutic approaches.

Keywords: KCNH1; Induced pluripotent stem cells; Temple–Baraitser syndrome; ZimmermannLaband syndrome.

MeSH terms

  • Abnormalities, Multiple* / genetics
  • Craniofacial Abnormalities*
  • Ether-A-Go-Go Potassium Channels / genetics
  • Female
  • Fibromatosis, Gingival*
  • Hallux / abnormalities*
  • Hand Deformities, Congenital*
  • Humans
  • Induced Pluripotent Stem Cells*
  • Intellectual Disability* / genetics
  • Mutation
  • Nails, Malformed*
  • Thumb / abnormalities*

Substances

  • KCNH1 protein, human
  • Ether-A-Go-Go Potassium Channels

Supplementary concepts

  • Temple-Baraitser Syndrome
  • Zimmerman Laband syndrome