Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Haploinsufficiency of ARHGAP42 is associated with hypertension

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Atrial fibrillation-a complex polygenetic disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Direct to consumer genetic testing in Denmark-public knowledge, use, and attitudes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Forming and ending marital or cohabiting relationships in a Danish population-based cohort of individuals with neurofibromatosis 1

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Case report: ‘AARS2 leukodystrophy’

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Trisomy 8 mosaicism in the placenta: A Danish cohort study of 37 cases and a literature review

    Research output: Contribution to journalReviewpeer-review

  3. Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Family studies have established that the heritability of blood pressure is significant and genome-wide association studies (GWAS) have identified numerous susceptibility loci, including one within the non-coding part of Rho GTPase-activating protein 42 gene (ARHGAP42) on chromosome 11q22.1. Arhgap42-deficient mice have significantly elevated blood pressure, but the phenotypic effects of human variants in the coding part of the gene are unknown. In a Danish cohort of carriers with apparently balanced chromosomal rearrangements, we identified a family where a reciprocal translocation t(11;18)(q22.1;q12.2) segregated with hypertension and obesity. Clinical re-examination revealed that four carriers (age 50-77 years) have had hypertension for several years along with an increased body mass index (34-43 kg/m2). A younger carrier (age 23 years) had normal blood pressure and body mass index. Mapping of the chromosomal breakpoints with mate-pair and Sanger sequencing revealed truncation of ARHGAP42. A decreased expression level of ARHGAP42 mRNA in the blood was found in the translocation carriers relative to controls and allele-specific expression analysis showed monoallelic expression in the translocation carriers, confirming that the truncated allele of ARHGAP42 was not expressed. These findings support that haploinsufficiency of ARHGAP42 leads to an age-dependent hypertension. The other breakpoint truncated a regulatory domain of the CUGBP Elav-like family member 4 (CELF4) gene on chromosome 18q12.2 that harbours several GWAS signals for obesity. We thereby provide additional support for an obesity locus in the CELF4 domain.

Original languageEnglish
JournalEuropean journal of human genetics : EJHG
Volume27
Issue number8
Pages (from-to)1296-1303
Number of pages8
ISSN1018-4813
DOIs
Publication statusPublished - 1 Aug 2019

ID: 57062883