Browsing by Author "Abinun, Mario"

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    Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations
    (Cell Press, 2008-07) Guerrini, Matteo M.; Sobacchi, Cristina; Cassani, Barbara; Abinun, Mario; Pangrazio, Alessandra; Moratto, Daniele; Mazzolari, Evelina; Clayton-Smith, Jill; Orchard, Paul; Coxon, Fraser P.; Helfrich, Miep H.; Crocket, Julie C.; Mellis, David; Vellod, Ashok; Tezcan, İlhan; Notarangelo, Luigi D.; Rogers, Michael J.; Vezzoni, Paolo; Villa, Anna; Frattini, Annalisa; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Çocuk İmmunoloji Bilim Dalı.; AAH-1658-2021; 34975059200
    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.
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    Mutations in the signal transducer and activator of transcription 3 (STAT3) and diagnostic guidelines for the Hyper-IgE Syndrome
    (Wiley, 2010-04) Woellner, Cristina; Gertz, M. E.; Schaffer, Alejandro; Lagos, Macarena; Perro, Mario; Glocker, Erik-Oliver; Pietrogrande, Maria Cristina; Cossu, Fausto; Marin Franco, Jose Luis; Matamoros, N.; Pietrucha, Bernard; Heropolitanska-Pliszka, Edyta; Yeganch, M.; Rezaei, Nima; Espanol, Teresa; Ehl, Stephan; Gennery, Andrew R.; Abinun, Mario; Breborowicz, Anna; Niehues, Tim; Junker, Anne K.; Turvey, Stuart E.; Plebani, Alessandro; Sanchez, Berta Erika Luis; Garty, Ben Zion; Pignata, Claudio; Cancrini, Caterina; Litzman, Jiří; Sanal, Özden; Batimann, U.; Bacchetta, Rosa; Hsu, Amy P.; Davis, Joie N.; Hammarström, Lennart L.G.; Davis, Edward Graham; Eren, Efrem; Arkwright, Peter D.; Moilanen, Jukka S.; Viemann, Dorothee; Khan, Sujoy; Máródi, László D.R.; Cant, Andrew James; Freeman, Alexandra F.; Puck, Jennifer M.; Holland, Steven M.; Grimbacher, Bodo; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; AAH-1658-2021