Article Text

Download PDFPDF
Original article
Decreased telomere length in children with cartilage-hair hypoplasia
  1. Svetlana Kostjukovits1,2,
  2. Sofie Degerman3,
  3. Minna Pekkinen2,
  4. Paula Klemetti1,
  5. Mattias Landfors3,
  6. Göran Roos3,
  7. Mervi Taskinen1,
  8. Outi Mäkitie1,2,4
  1. 1Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  2. 2Folkhälsan Research Center, Helsinki, Finland
  3. 3Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
  4. 4Center for Molecular Medicine, Karolinska Institutet and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to Dr Outi Mäkitie, Folkhälsan Institute of Genetics, PO Box 63, FIN-00014 University of Helsinki, Helsinki, 00014, Finland; outi.makitie{at}


Background Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia caused by RMRP (RNA component of mitochondrial RNA processing endoribonuclease) gene mutations. Manifestations include short stature, variable immunodeficiency, anaemia and increased risk of malignancies, all of which have been described also in telomere biology disorders. RMRP interacts with the telomerase RT (TERT) subunit, but the influence of RMRP mutations on telomere length is unknown. We measured relative telomere length (RTL) in patients with CHH, their first-degree relatives and healthy controls and correlated RTL with clinical and laboratory features.

Methods The study cohort included 48 patients with CHH with homozygous (n=36) or compound heterozygous RMRP mutations (median age 38.2 years, range 6.0–70.8 years), 86 relatives (74 with a heterozygous RMRP mutation) and 94 unrelated healthy controls. We extracted DNA from peripheral blood, sequenced the RMRP gene and measured RTL by qPCR.

Results Compared with age-matched and sex-matched healthy controls, median RTL was significantly shorter in patients with CHH (n=40 pairs, 1.05 vs 1.21, p=0.017), but not in mutation carriers (n=48 pairs, 1.16 vs 1.10, p=0.224). RTL correlated significantly with age in RMRP mutation carriers (r=−0.482, p<0.001) and non-carriers (r=−0.498, p<0.001), but not in patients (r=−0.236, p=0.107). In particular children (<18 years) with CHH had shorter telomeres than controls (median RTL 1.12 vs 1.26, p=0.008). In patients with CHH, RTL showed no correlation with genotype, clinical or laboratory characteristics.

Conclusions Telomere length was decreased in children with CHH. We found no correlation between RTL and clinical or laboratory parameters.

  • Bone marrow failure
  • relative telomere length
  • RMRP
  • telomerase
  • telomere biology disorders

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors Study design: PK, MT, GR and OM. Study conduct: SK, MP, SD. Data collection: SK. Data analysis: SK, SD, ML. Data interpretation: SK, SD, MT, GR, OM. Drafting manuscript: SK. Revising manuscript content: all authors. Approving final version of manuscript: all authors.

  • Funding This work was supported by the Sigrid Jusélius Foundation (to OM); the Academy of Finland (to OM); the Folkhälsan Research Foundation (to OM); the Helsinki University Hospital Research Funds (to OM and MT); the Foundation for Pediatric Research (to OM and MT); the Swedish Childhood Cancer Foundation (to OM and SD); the Lion's Cancer Foundation in Umeå (to SD and GR); the Doctoral School in Health Sciences at the University of Helsinki (to SK); the Swedish Cancer Research Foundation (to GR) and the Västerbotten County Council (to GR and SD).

  • Competing interests None.

  • Ethics approval The research ethics committee at Helsinki University Hospital, Finland.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Detailed data on the methods used in this study are available upon request from the corresponding author.