Translational and clinical immunologyDefects in lymphocyte telomere homeostasis contribute to cellular immune phenotype in patients with cartilage-hair hypoplasia
Graphical abstract
Section snippets
Ethical statement and patients' characteristics
All samples from patients with CHH and their relatives were obtained with informed consent and approval of local ethical review boards in accordance with the Declaration of Helsinki. The patients were cared for at the Clinic for Special Children in Strasburg, Pennsylvania. Clinical and molecular studies were performed with oversight from the Lancaster General Hospital Institutional Review Board. All reported subjects underwent laboratory and molecular testing, as previously described.14 The
Results
Thymic and T-lymphocyte functions from 5 of the 15 patients with CHH (UPN2, UPN3, and UPN6-UPN8) have been previously reported and demonstrated reduced thymic output, reduced or delayed cell-cycle progression, and a moderate increase in apoptosis19 compared with healthy subjects. All subjects studied in this report were heterozygous carriers or homozygous for lncRNA RMRP n.70 A>G (see the diagram of RMRP folding prediction in Fig 120).
Discussion
Patients with CHH display some clinical features that overlap with telomere biology disorders and are particularly susceptible to immune deficiency. Interestingly, both disorders are categorized as diseases with a significant risk of bone marrow failure and have been considered to belong to disease groups, including bone marrow failure syndromes, primary immunodeficiencies,25 and ribosomopathies.26
Model studies of CHH have been challenging thus far because of the essential functions of lncRNA
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Cited by (0)
Work in the Lansdorp laboratory is supported by grants from the Canadian Institutes of Health Research (MOP38075 and GMH79042). N.L.R. worked at the Clinic for Special Children, Strasburg, Pennsylvania, during the majority of this work.
Disclosure of potential conflict of interest: G. Aubert is employed by Repeat Diagnostics. P. M. Lansdorp is employed by Canadian Institutes of Health Research (MOP38075 and GMH79042) and has received stock options from Repeat Diagnostics. N. L. Rider is employed by Baylor College of Medicine and receives royalties from UpToDate. K. A. Strauss declares that he has no relevant conflicts of interest.