Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations
| Autor: | Paolo Vezzoni, David Mellis, Julie C. Crockett, Fraser P. Coxon, Alessandra Pangrazio, Daniele Moratto, Evelina Mazzolari, Anna Villa, Mario Abinun, Paul J. Orchard, Jill Clayton-Smith, Luigi D. Notarangelo, Ilhan Tezcan, Michael J. Rogers, Barbara Cassani, Sara Sebnem Kilic, Miep H. Helfrich, Annalisa Frattini, Ashok Vellodi, Cristina Sobacchi, Matteo M Guerrini |
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| Přispěvatelé: | Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Çocuk İmmunoloji Bilim Dalı., Kılıç, Sara Şebnem, AAH-1658-2021, Çocuk Sağlığı ve Hastalıkları |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Turkey DNA Mutational Analysis Gene sequence Monocyte Hypogammaglobulinemia Consanguinity Receptor activator differentiation Agammaglobulinemia Genetics(clinical) Priority Cell proliferation Genetics & Heredity Mutation Colony stimulating factor 1 Antigens CD45 Pedigree Autosomal recessive osteopetrosis Cohort studies Osteoclast Osteopetrosis Osteopetrosis with Renal Tubular Acidosis Chloride Channels Leukocytes mononuclear Human musculoskeletal diseases Albers Schoenberg disease Cells Argentina Radiography thoracic Receptors vitronectin Article Ilium Genetic Genetics Humans Polymorphism Receptor activator of nuclear factor-kappa B RANK ligand Polymorphism Genetic medicine.disease Cell line transformed Immunology İmmunological parameters Nucleotide sequence Lipopolysaccharides Herpesvirus 4 Human Journal Amino acid substitution Mutation missense Duplication Biopsy Osteoimmunology Osteoclasts medicine.disease_cause Disease Pakistan İmmunoglobulin deficiency Genetics (clinical) Tartrate-resistant acid phosphatase biology Macrophage colony-stimulating factor Homozygote Isoenzymes medicine.anatomical_structure RANKL Female Osteoclast differentiation factor Alele Cells cultured Heterozygote Sibling İmmune system Genes Recessive Case-control studies Sequence homology amino Acid Arginine Cell transformation viral Amino acid sequence Receptor activator of nuclear factor kappa B Molecular sequence data medicine Acid phosphatase Cysteine Gene mutation Human tissue B lymphocyte Tartrate-Resistant Acid Phosphatase Models immunological İmmune deficiency Osteoprotegerin In vitro study Dendrites TCIRG1 Actins biology.protein Leukocyte Common Antigens CLCN7 Protein structure tertiary |
| Zdroj: | American journal of human genetics 83 (2008): 64–76. doi:10.1016/j.ajhg.2008.06.015 info:cnr-pdr/source/autori:Guerrini MM; Sobacchi C; Cassani B; Abinun M; Kilic SS; Pangrazio A; Moratto D; Mazzolari E; Clayton-Smith J; Orchard P; Coxon FP; Helfrich MH; Crockett JC; Mellis D; Vellodi A; Tezcan I; Notarangelo LD; Rogers MJ; Vezzoni P; Villa A; Frattini A./titolo:Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations./doi:10.1016%2Fj.ajhg.2008.06.015/rivista:American journal of human genetics/anno:2008/pagina_da:64/pagina_a:76/intervallo_pagine:64–76/volume:83 |
| DOI: | 10.1016/j.ajhg.2008.06.015 |
| Popis: | Autosomal-Recessive Osteopetrosis (ARO) comprises a heterogeneous group of bone diseases for which mutations in five genes are known as causative. Most ARO are classified as osteoclast-rich, but recently a subset of osteoclast-poor ARO has been recognized as due to a defect in TNESF11 (also called RANKL or TRANCE, coding for the RANKL protein), a master gene driving osteoclast differentiation along the RANKL-RANK axis. RANKL and RANK (coded for by the TNFRSF11A gene) also play a role in the immune system, which raises the possibility that defects in this pathway might cause osteopetrosis with immunodeficiency. From a large series of ARO patients we selected a Turkish consanguineous family with two siblings affected by ARO and hypogammaglobulinemia with no defects in known osteopetrosis genes. Sequencing of genes involved in the RANKL downstream pathway identified a homozygous mutation in the TNERSF11A gene in both siblings. Their monocytes failed to differentiate in vitro into osteoclasts upon exposure to M-CSF and RANKL, in keeping with an osteoclast-intrinsic defect. Immunological analysis showed that their hypogammaglobulinemia was associated with impairment in immunoglobulin-secreting B cells. Investigation of other patients revealed a defect in both TNFRSF11A alleles in six additional, unrelated families. Our results indicate that TNFRSF11A mutations can cause a clinical condition in which severe ARO is associated with an immunoglobulin-production defect. Chief Scientist Office (CZB/4/495) |
| Databáze: | OpenAIRE |
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