Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
HELLP babies link a novel lincRNA to the trophoblast cell cycle
Marie van Dijk, … , Augusta M.A. Lachmeijer, Cees B.M. Oudejans
Marie van Dijk, … , Augusta M.A. Lachmeijer, Cees B.M. Oudejans
Published October 24, 2012
Citation Information: J Clin Invest. 2012;122(11):4003-4011. https://doi.org/10.1172/JCI65171.
View: Text | PDF
Research Article

HELLP babies link a novel lincRNA to the trophoblast cell cycle

  • Text
  • PDF
Abstract

The HELLP syndrome is a pregnancy-associated disease inducing hemolysis, elevated liver enzymes, and low platelets in the mother. Although the HELLP symptoms occur in the third trimester in the mother, the origin of the disease can be found in the first trimester fetal placenta. A locus for the HELLP syndrome is present on chromosome 12q23 near PAH. Here, by multipoint nonparametric linkage, pedigree structure allele sharing, and haplotype association analysis of affected sisters and cousins, we demonstrate that the HELLP locus is in an intergenic region on 12q23.2 between PMCH and IGF1. We identified a novel long intergenic noncoding RNA (lincRNA) transcript of 205,012 bases with (peri)nuclear expression in the extravillous trophoblast using strand-specific RT-PCR complemented with RACE and FISH. siRNA-mediated knockdown followed by RNA-sequencing, revealed that the HELLP lincRNA activated a large set of genes that are involved in the cell cycle. Furthermore, blocking potential mutation sites identified in HELLP families decreased the invasion capacity of extravillous trophoblasts. This is the first large noncoding gene to be linked to a Mendelian disorder with autosomal-recessive inheritance.

Authors

Marie van Dijk, Hari K. Thulluru, Joyce Mulders, Omar J. Michel, Ankie Poutsma, Sandra Windhorst, Gunilla Kleiverda, Daoud Sie, Augusta M.A. Lachmeijer, Cees B.M. Oudejans

×

Figure 1

Identification of the HELLP locus on chromosome 12q23.2.

Options: View larger image (or click on image) Download as PowerPoint
Identification of the HELLP locus on chromosome 12q23.2.
Multipoint nonp...
Multipoint nonparametric linkage analysis (A; see also Supplemental File 1), pedigree structure analysis with SNP/INDEL markers (B; see also Supplemental File 2), and HaploView analysis (C) defined the HELLP locus region as residing in a intergenic region of about 170 kb between C12orf48 and IGF1 on 12q23.2.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts