title: Decreased telomere length in children with cartilage-hair hypoplasia.
abstract: Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia caused byRMRP(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.RMRPinteracts with the telomerase RT (TERT) subunit, but the influence ofRMRPmutations 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.
  
  
  
  The study cohort included 48 patients with CHH with homozygous (n=36) or compound heterozygousRMRPmutations (median age 38.2 years, range 6.0-70.8 years), 86 relatives (74 with a heterozygousRMRPmutation) and 94 unrelated healthy controls. We extracted DNA from peripheral blood, sequenced theRMRPgene and measured RTL by qPCR.
  
  
  
  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 inRMRPmutation 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.
  
  
  
  Telomere length was decreased in children with CHH. We found no correlation between RTL and clinical or laboratory parameters.
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Kostjukovits
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Degerman
authors.affiliation: Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Pekkinen
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Klemetti
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Landfors
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Taskinen
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Folkhälsan Research Center, Helsinki, Finland.|Center for Molecular Medicine, Karolinska Institutet and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D004722:Endoribonucleases / Q000235:genetics; D005260:Female; D006197:Hair / Q000002:abnormalities*; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D009154:Mutation / Q000235:genetics; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000235:genetics; D000081207:Primary Immunodeficiency Diseases; D059505:Telomere Homeostasis; D055815:Young Adult
chemical_list: D004722:Endoribonucleases; C058330:mitochondrial RNA-processing endoribonuclease
keywords: Bone marrow failure; RMRP; relative telomere length; telomerase; telomere biology disorders