Immune deficiencies, infection, and systemic immune disordersReduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia
Section snippets
Patients
Eighteen subjects with typical features of CHH (skeletal and hair abnormalities) were included in the study (mean age, 10.9 years; range, 1.0-21.0 years). Of these, 13 belonged to the Amish population in Pennsylvania. Deidentified information on clinical history was obtained for all patients from the referring physicians. Blood was collected from patients and controls by venipuncture. Informed consent was obtained from patients and parents in accordance with the local Institutional Review Board
Description of the clinical phenotype and genotype
We analyzed a cohort of 18 patients with clinical diagnosis of CHH and genetically confirmed RMRP mutations. Clinical features of a subgroup of the patients analyzed here were previously described in an Amish CHH cohort.16 Individual data on the clinical phenotypes are reported in Table I. Eleven patients had a history of severe and/or recurrent infections (n = 11), chronic diarrhea (n = 2), cytopenias (n = 3), and/or autoimmunity (n = 1). Three of these 11 patients had a clinical phenotype of
Discussion
Significant variability in the clinical phenotype has been reported in patients with RMRP mutations. There is some evidence that the type and level of RMRP functional impairment may correlate with the severity of the clinical spectrum. In particular, mutations that affect ribosomal RNA cleavage and ribosomal assembly are associated with more severe bone dysplasia, whereas mutations that reduce mRNA cleavage have a more significant impact on cell cycle regulation and are associated with a higher
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Cited by (36)
Shorter birth length and decreased T-cell production and function predict severe infections in children with non–severe combined immunodeficiency cartilage–hair hypoplasia
2024, Journal of Allergy and Clinical Immunology: GlobalEarly prenatal presentation of the cartilage-hair hypoplasia / anauxetic dysplasia spectrum of disorders mimicking recurrent thanatophoric dysplasia
2021, European Journal of Medical GeneticsCitation Excerpt :Mäkitie identified lymphopenia in 62% of a large cohort of patients with CHH (Mäkitie, 1992). It has been found that RMRP mutations have a profound effect on lymphocyte maturation and function and they induce increased apoptosis of T cells and interfere with thymic generation of T lymphocytes (de la Fuente et al., 2011; Pierce and Polmar, 1982). There have been two previous reports of fetal identification of CHH (Crahes et al., 2013; Lam et al., 2006).
Common presentations and diagnostic approaches
2020, Stiehm's Immune Deficiencies: Inborn Errors of ImmunityDefects in lymphocyte telomere homeostasis contribute to cellular immune phenotype in patients with cartilage-hair hypoplasia
2017, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Additionally, recent evidence suggests a role for posttranscriptional RNA processing by lnc RMRP, affecting gene regulation in disparate cellular functional pathways involved in CHH, such as skeletal development and hematopoietic cell proliferation,32 which can also contribute to the phenotype we have observed. We have shown a proliferation delay or failure in stimulated lymphocytes, which is consistent with previous observations.19 In contrast to telomerase expression and activity detected in vitro from cell extracts, loading of the telomerase holoenzyme to the telomere end and repeat addition is cell-cycle dependent.
Analysis of clinical and immunologic phenotype in a large cohort of children and adults with cartilage-hair hypoplasia
2017, Journal of Allergy and Clinical ImmunologyHigh prevalence of bronchiectasis in patients with cartilage-hair hypoplasia
2017, Journal of Allergy and Clinical Immunology
Supported by the Manton Foundation. M. Recher was supported by the Swiss National Science Foundation (SSMB; grant PASMP3-127678/1). M. Adair was supported by a fellowship from Talecris Biotherapeutics.
Disclosure of potential conflict of interest: F. A. Bonilla receives research support from Talecris Biotherapeutics, has consultant arrangements with ENTRA Pharmaceuticals and CSL Behring, receives royalties from UpToDate, and is an advisor for the Immune Deficiency Foundation. H. D. Ochs has served on the advisory board for Baxter and receives research support from the NIH, the Jeffrey Modell Foundation, and CSL Behring. The rest of the authors have declared that they have no conflict of interest.
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These authors contributed equally to this work.