Immunodeficiency in cartilage-hair hypoplasia: Pathogenesis, clinical course and management.
RMRP
chondrodysplasia
combined immunodeficiency
Journal
Scandinavian journal of immunology
ISSN: 1365-3083
Titre abrégé: Scand J Immunol
Pays: England
ID NLM: 0323767
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
27
04
2020
revised:
20
05
2020
accepted:
29
05
2020
pubmed:
9
6
2020
medline:
10
10
2020
entrez:
8
6
2020
Statut:
ppublish
Résumé
Cartilage-hair hypoplasia (CHH) is an autosomal recessive syndromic immunodeficiency with skeletal dysplasia, short stature, hypotrichosis, variable degree of immune dysfunction and increased incidence of anaemia, Hirschsprung disease and malignancy. CHH is caused by variants in the RMRP gene, encoding the untranslated RNA molecule of the mitochondrial RNA-processing endoribonuclease, which participates in for example cell cycle regulation and telomere maintenance. Recent studies have expanded our understanding of the complex pathogenesis of CHH. Immune dysfunction has a major impact on clinical course and prognosis. Clinical features of immune dysfunction are highly variable, progressive and include infections, lung disease, immune dysregulation and malignancy. Mortality is increased compared with the general population, due to infections, malignancy and pulmonary disease. Several risk factors for early mortality have been reported in the Finnish CHH cohort and can be used to guide management. Newborn screening for severe combined immunodeficiency can possibly be of prognostic value in CHH. Regular follow-up by a multidisciplinary team should be implemented to address immune dysfunction in all patients with CHH, also in asymptomatic cases. Haematopoietic stem cell transplantation can cure immune dysfunction, but its benefits in mildly symptomatic patients with CHH remain debatable. Further research is needed to understand the mechanisms behind the variability of clinical features, to search for potential molecular treatment targets, to examine and validate risk factors for early mortality outside the Finnish CHH cohort and to develop management guidelines. This review focuses on the pathogenesis, clinical course and management of CHH.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12913Subventions
Organisme : Sigrid Jusélius Foundation
Organisme : Academy of Finland
Organisme : Folkhälsan Research Foundation
Organisme : Novo Nordisk Foundation
Organisme : Helsinki University Hospital Research Funds
Organisme : Swedish Childhood Cancer Foundation
Organisme : Foundation for Pediatric Research
Informations de copyright
© 2020 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.
Références
Maroteaux SP, Savart P, Lefebvre J, et al. Les formes partielles de la dysostose metaphysaire. Presse Med. 1983;1963(30):1523-1526.
McKusick VA, Eldridge R, Hostetler JA, et al. DWARFISM IN THE AMISH. II. CARTILAGE-HAIR HYPOPLASIA. Bull Johns Hopkins Hosp. 1965;116:285-326.
Makitie O. Cartilage-hair hypoplasia in Finland: epidemiological and genetic aspects of 107 patients. J Med Genet. 1992;29(9):652-655.
Makitie O, Kaitila I. Cartilage-hair hypoplasia-clinical manifestations in 108 Finnish patients. Eur J Pediatr. 1993;152(3):211-217.
Makitie O, Pukkala E, Kaitila I. Increased mortality in cartilage-hair hypoplasia. Arch Dis Child. 2001;84(1):65-67.
Williams MS, Ettinger RS, Hermanns P, et al. The natural history of severe anemia in cartilage-hair hypoplasia. Am J Med Genet A. 2005;138(1):35-40.
Taskinen M, Ranki A, Pukkala E, et al. Extended follow-up of the Finnish cartilage-hair hypoplasia cohort confirms high incidence of non-Hodgkin lymphoma and basal cell carcinoma. Am J Med Genet A. 2008;146a(18):2370-2375.
Ridanpaa M, van Eenennaam H, Pelin K, et al. Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell. 2001;104(2):195-203.
Thiel CT, Horn D, Zabel B, et al. Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. Am J Hum Genet. 2005;77(5):795-806.
Vakkilainen S, Skoog T, Einarsdottir E, et al. The human long non-coding RNA gene RMRP has pleiotropic effects and regulates cell-cycle progression at G2. Sci Rep. 2019;9(1):13758.
Hermanns P, Bertuch AA, Bertin TK, et al. Consequences of mutations in the non-coding RMRP RNA in cartilage-hair hypoplasia. Hum Mol Genet. 2005;14(23):3723-3740.
Mattijssen S, Welting TJ, Pruijn GJ. RNase MRP and disease. Wiley interdiscip rev. 2010;1(1):102-116.
Welting TJ, van Venrooij WJ, Pruijn GJ. Mutual interactions between subunits of the human RNase MRP ribonucleoprotein complex. Nucleic Acids Res. 2004;32(7):2138-2146.
Sun X, Zhang R, Liu M, et al. Rmrp mutation disrupts chondrogenesis and bone ossification in zebrafish model of cartilage-hair hypoplasia via enhanced Wnt/β-catenin signaling. J Bone Miner Res. 2019;34(11):2101-2116.
Ridanpaa M, Sistonen P, Rockas S, et al. Worldwide mutation spectrum in cartilage-hair hypoplasia: ancient founder origin of the major70A->G mutation of the untranslated RMRP. Eur J Hum Genet. 2002;10(7):439-447.
Hirose Y, Nakashima E, Ohashi H, et al. Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia. J Hum Genet. 2006;51(8):706-710.
Gomes ME, Calatrava Paternostro L, Moura VR, et al. Identification of novel and recurrent RMRP variants in a series of Brazilian patients with cartilage-hair hypoplasia: McKusick Syndrome. Mol Syndromol. 2020;10(5):255-263.
Taskinen M, Mäkitie O. Cartilage-hair hypoplasia-much more than growth problem. Duodecim. 2011;127(3):273-279.
Nakashima E, Tran JR, Welting TJ, et al. Cartilage hair hypoplasia mutations that lead to RMRP promoter inefficiency or RNA transcript instability. Am J Med Genet A. 2007;143a(22):2675-2681.
Welting TJ, Mattijssen S, Peters FM, et al. Cartilage-hair hypoplasia-associated mutations in the RNase MRP P3 domain affect RNA folding and ribonucleoprotein assembly. Biochim Biophys Acta. 2008;1783(3):455-466.
Kavadas FD, Giliani S, Gu Y, et al. Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations. J Allergy Clin Immunol. 2008;122(6):1178-1184.
Glazov EA, Zankl A, Donskoi M, et al. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia. PLoS Genet. 2011;7(3):e1002027.
Narayanan DL, Shukla A, Kausthubham N, et al. An emerging ribosomopathy affecting the skeleton due to biallelic variations in NEPRO. Am J Med Genet A. 2019;179(9):1709-1717.
Rogler LE, Kosmyna B, Moskowitz D, et al. Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage-hair hypoplasia. Hum Mol Genet. 2014;23(2):368-382.
Juvonen E, Makitie O, Makipernaa A, et al. Defective in-vitro colony formation of haematopoietic progenitors in patients with cartilage-hair hypoplasia and history of anaemia. Eur J Pediatr. 1995;154(1):30-34.
de la Fuente MA, Recher M, Rider NL, et al. Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. 2011;128(1):139-146.
Goldfarb KC, Cech TR. Targeted CRISPR disruption reveals a role for RNase MRP RNA in human preribosomal RNA processing. Genes Dev. 2017;31(1):59-71.
Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458-460.
Morin GB. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell. 1989;59(3):521-529.
Bertuch AA. The molecular genetics of the telomere biology disorders. RNA Biol. 2016;13(8):696-706.
Maida Y, Yasukawa M, Furuuchi M, et al. An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature. 2009;461(7261):230-235.
Kostjukovits S, Degerman S, Pekkinen M, et al. Decreased telomere length in children with cartilage-hair hypoplasia. J Med Genet. 2017;54(5):365-370.
Aubert G, Strauss KA, Lansdorp PM, et al. Defects in lymphocyte telomere homeostasis contribute to cellular immune phenotype in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. 2017;140(4):1120-1129.e1121.
Vulliamy T, Marrone A, Goldman F, et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature. 2001;413(6854):432-435.
Savage SA. Dyskeratosis congenita. In: Adam MP, Ardinger HH, Pagon RA, et al., GeneReviews((R)). Seattle, WA: University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved; 1993.
Alder JK, Hanumanthu VS, Strong MA, et al. Diagnostic utility of telomere length testing in a hospital-based setting. Proc Natl Acad Sci USA. 2018;115(10):E2358-E2365.
Wagner CL, Hanumanthu VS, Talbot CC Jr, et al. Short telomere syndromes cause a primary T cell immunodeficiency. J Clin Investig. 2018;128(12):5222-5234.
Kostjukovits S, Klemetti P, Valta H, et al. Analysis of clinical and immunologic phenotype in a large cohort of children and adults with cartilage-hair hypoplasia. J Allergy Clin Immunol. 2017;140(2):612-614.e615.
Rosenbluh J, Nijhawan D, Chen Z, et al. RMRP is a non-coding RNA essential for early murine development. PLoS One. 2011;6(10):e26270.
Bailly-Botuha C, Jaubert F, Taam RA, et al. Diffuse lymphoplasmacytic bronchiolitis in cartilage-hair hypoplasia. J Pediatr. 2008;152(3):429-433.
Horn J, Schlesier M, Warnatz K, et al. Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia. Hum Immunol. 2010;71(9):916-919.
Kostjukovits S, Klemetti P, Fohr A, et al. High prevalence of bronchiectasis in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. 2017;139(1):375-378.
Bordon V, Gennery AR, Slatter MA, et al. Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation. Blood. 2010;116(1):27-35.
Toiviainen-Salo S, Kajosaari M, Piilonen A, et al. Patients with cartilage-hair hypoplasia have an increased risk for bronchiectasis. J Pediatr. 2008;152(3):422-428.
Daheshia M, Prahl JD, Carmichael JJ, et al. The immune response and its therapeutic modulation in bronchiectasis. Pulm Med. 2012;2012:1-7.
Vakkilainen S, Taskinen M, Klemetti P, et al. A 30-year prospective follow-up study reveals risk factors for early death in cartilage-hair hypoplasia. Front Immunol. 2019;10:1581.
Kotaniemi JT, Pallasaho P, Sovijarvi AR, et al. Respiratory symptoms and asthma in relation to cold climate, inhaled allergens, and irritants: a comparison between northern and southern Finland. J Asthma. 2002;39(7):649-658.
Chang AB, Bush A, Grimwood K. Bronchiectasis in children: diagnosis and treatment. Lancet (London, England). 2018;392(10150):866-879.
Vakkilainen S, Makitie R, Klemetti P, et al. A wide spectrum of autoimmune manifestations and other symptoms suggesting immune dysregulation in patients with cartilage-hair hypoplasia. Front Immunol. 2018;9:2468.
Moshous D, Meyts I, Fraitag S, et al. Granulomatous inflammation in cartilage-hair hypoplasia: risks and benefits of anti-TNF-alpha mAbs. J Allergy Clin Immunol. 2011;128(4):847-853.
Buchbinder D, Hauck F, Albert MH, et al. Rubella virus-associated cutaneous granulomatous disease: a unique complication in immune-deficient patients, not limited to DNA repair disorders. J Clin Immunol. 2019;39(1):81-89.
Taskinen M, Jeskanen L, Karjalainen-Lindsberg ML, et al. Combating cancer predisposition in association with idiopathic immune deficiency: a recurrent nodal and cutaneous T-cell lymphoproliferative disease in a patient with cartilage-hair hypoplasia. Clin Lymph Myelom Leuk. 2013;13(1):73-76.
Sathishkumar D, Gach JE, Ogboli M, et al. Cartilage hair hypoplasia with cutaneous lymphomatoid granulomatosis. Clin Exp Dermatol. 2018;43(6):713-717.
Biggs CM, Kostjukovits S, Dobbs K, et al. Diverse autoantibody reactivity in cartilage-hair hypoplasia. J Clin Immunol. 2017;37(6):508-510.
Poliani PL, Facchetti F, Ravanini M, et al. Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome. Blood. 2009;114(1):105-108.
Nguyen A, Martin Silva N, de Boysson H, et al. Diffuse large B-cell lymphoma chemotherapy reveals a combined immunodeficiency syndrome in cartilage hair hypoplasia. Swiss Med Wkly. 2018;148:w14606.
Hauck F, Voss R, Urban C, et al. Intrinsic and extrinsic causes of malignancies in patients with primary immunodeficiency disorders. J Allergy Clin Immunol. 2018;141(1):59-68.e54.
Verhoeven D, Stoppelenburg AJ, Meyer-Wentrup F, et al. Increased risk of hematologic malignancies in primary immunodeficiency disorders: opportunities for immunotherapy. Clin Immunol (Orlando, Fla). 2018;190:22-31.
Holopainen E, Vakkilainen S, Mäkitie O. Gynecologic assessment of 19 adult females with cartilage-hair hypoplasia - high rate of HPV positivity. Orphanet J Rare Dis. 2018;13(1):207.
Klemetti P, Valta H, Kostjukovits S, et al. Cartilage-hair hypoplasia with normal height in childhood-4 patients with a unique genotype. Clin Genet. 2017;92(2):204-207.
Ip W, Gaspar HB, Kleta R, et al. Variable phenotype of severe immunodeficiencies associated with RMRP gene mutations. J Clin Immunol. 2015;35(2):147-157.
Rider NL, Morton DH, Puffenberger E, et al. Immunologic and clinical features of 25 Amish patients with RMRP 70 A->G cartilage hair hypoplasia. Clin Immunol (Orlando, Fla). 2009;131(1):119-128.
Makitie O, Kaitila I, Savilahti E. Susceptibility to infections and in vitro immune functions in cartilage-hair hypoplasia. Eur J Pediatr. 1998;157(10):816-820.
Makitie O, Kaitila I, Savilahti E. Deficiency of humoral immunity in cartilage-hair hypoplasia. J Pediatr. 2000;137(4):487-492.
Kainulainen L, Lassila O, Ruuskanen O. Cartilage-hair hypoplasia: follow-up of immunodeficiency in two patients. J Clin Immunol. 2014;34(2):256-259.
Makitie O, Heikkinen M, Kaitila I, et al. Hirschsprung's disease in cartilage-hair hypoplasia has poor prognosis. J Pediatr Surg. 2002;37(11):1585-1588.
Scott EM, Chandra S, Li J, et al. Abnormal Newborn screening follow-up for severe combined immunodeficiency in an amish cohort with cartilage-hair hypoplasia. J Clin Immunol. 2020;40(2):321-328.
Bonafe L, Schmitt K, Eich G, et al. RMRP gene sequence analysis confirms a cartilage-hair hypoplasia variant with only skeletal manifestations and reveals a high density of single-nucleotide polymorphisms. Clin Genet. 2002;61(2):146-151.
Vakkilainen S, Costantini A, Taskinen M, et al. 'Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations. J Med Genet. 2020;57(1):18-22.
Faitelson Y, Manson D. Cartilage-hair hypoplasia: a spectrum of clinical and radiological findings. LymphoSign J. 2015;2(3):157-164.
Kamani NR, Kumar S, Hassebroek A, et al. Malignancies after hematopoietic cell transplantation for primary immune deficiencies: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2011;17(12):1783-1789.
Hermanns P, Tran A, Munivez E, et al. RMRP mutations in cartilage-hair hypoplasia. Am J Med Genet A. 2006;140(19):2121-2130.