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Immunology (primary Immunodeficiency Syndromes
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephan Strobel, Alison M. Jones
Cartilage hair hypoplasia (CHH) is an autosomal recessive disorder that usually results in short-limb skeletal dysplasia, sometimes associated with T-cell and B-cell deficiencies. It is caused by mutations of the RMRP gene (RNA component of mitochondrial RNA processing endoribonuclease) on chromosome 9p12.
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Genetics: autosomal recessive disorder due to mutations in RMRP, encoding the untranslated RNA subunit of the ribonucleoprotein endoribonuclease (RNase MRP); CHH-associated mutations lead to decreased cell growth by impairing ribosomal assembly and by altering cyclin-dependent cell cycle regulation.
The role of systemic corticosteroids in severe asthma and new evidence in their management and tapering
Published in Expert Review of Clinical Immunology, 2021
Francesco Menzella, Giulia Ghidoni, Matteo Fontana, Silvia Capobelli, Francesco Livrieri, Claudia Castagnetti, Nicola Facciolongo
Regarding the role of biomarkers, an in vitro study evaluated the role of the long non-coding RNA component (lncRNA) of mitochondrial RNA processing endoribonuclease (RMRP) in an ovalbumin-induced asthmatic mouse model (OVA). The results showed that administration of RMRP overexpression in airway smooth muscle cells (ASMCs) increased biomarker levels in asthma [26]. Adhesion molecules play essential roles in transendothelial extravasation of T cells during inflammation. One study showed that CD8 + CD28 + TCRαβ + CD62LhighFoxP3bright T cells are present in lower numbers in the blood of some asthma patients, but they are abundant in others. These data highlight that asthma phenotypes can be further stratified into micro-subtypes with unique cellular and molecular characteristics, supporting the concept of asthma endotypes [27].
Advances in genetic and molecular understanding of Omenn syndrome - implications for the future
Published in Expert Opinion on Orphan Drugs, 2018
Whilst the relationship between Omenn syndrome and missense RAG mutations was clear, there were still some patients for whom a genetic diagnosis was unresolved. One report described five infants with Omenn syndrome, from four unrelated families, only two of whom had mutations in RAG1 [55]. Three other patients with similar clinical phenotypes had RAG gene polymorphisms, predicted not to affect endonuclease function. This suggested that mutations in other genes may mimic the Omenn syndrome clinical phenotype. A further report investigated seven cases of Omenn syndrome with appropriate clinic-immunophenotype in whom no defect in RAG genes had been found. All patients demonstrated absent TCRVB families; six had predominant TCRVB families, six had oligoclonal TCR gene rearrangements including TCRGD rearrangements [56]. The clinical phenotype has now been described in other VDJ recombination defects, including patients with mutations in DCLRE1C leading to Artemis deficiency [57], and in LIG4, which codes for DNA ligase 4 [58]. To date, patients with Omenn syndrome have now been described in most genetic forms of SCID including IL2Rγ deficiency, IL7Rα deficiency, adenosine deaminase deficiency, AK2 deficiency, haploinsufficiency of 22q11 causing DiGeorge syndrome, haploinsufficiency of CHD7 causing CHARGE syndrome, and defects in RMRP associated with cartilage hair hypoplasia [59–67]. However, the most commonly identified genetic defects are in the RAG1 and RAG2 genes.
Ribosomopathies and cancer: pharmacological implications
Published in Expert Review of Clinical Pharmacology, 2022
Gazmend Temaj, Sarmistha Saha, Shpend Dragusha, Valon Ejupi, Brigitta Buttari, Elisabetta Profumo, Lule Beqa, Luciano Saso
11) Cartilage-hair hypoplasia (CHH) is a disorder of bone growth characterized by short stature with other skeletal abnormalities, sparse hair, and abnormal immune system function. People affected by CHH have short limbs and long bones in their arms and legs, respectively. Mutations in RMRP are known to cause CHH. Unlike many other genes, the RMRP gene does not contain instructions for synthesizing a specific protein. RMRP participates in non-coding RNA synthesis. Subsequently, this RNA is involved in different processes and forms an enzyme complex called mitochondrial RNA-processing endonuclease (RNase MRP). RNase MRP is involved in RNA processing, which is required to assemble building blocks into functional proteins [43,282–285].