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Refinement of the clinical and mutational spectrum of UBE2A deficiency syndrome.
Cordeddu, Viviana; Macke, Erica L; Radio, Francesca Clementina; Lo Cicero, Stefania; Pantaleoni, Francesca; Tatti, Massimo; Bellacchio, Emanuele; Ciolfi, Andrea; Agolini, Emanuele; Bruselles, Alessandro; Brunetti-Pierri, Nicola; Suri, Mohnish; Josephs, Katherine S; McEntagart, Meriel; Lanpher, Brendan; Nickels, Katherine C; Haworth, Andrea; Reed, Laura; Cappuccio, Gerarda; Mammi, Isabella; Tarnowski, Jessica M; Novelli, Antonio; Melis, Daniela; Callewaert, Bert; Dallapiccola, Bruno; Klee, Eric; Tartaglia, Marco.
Afiliación
  • Cordeddu V; National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy.
  • Macke EL; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
  • Radio FC; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCSS, Rome, Italy.
  • Lo Cicero S; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Pantaleoni F; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCSS, Rome, Italy.
  • Tatti M; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Bellacchio E; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCSS, Rome, Italy.
  • Ciolfi A; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCSS, Rome, Italy.
  • Agolini E; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCSS, Rome, Italy.
  • Bruselles A; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  • Brunetti-Pierri N; Department of Translational Medicine, Federico II University of Naples, Naples, Italy.
  • Suri M; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
  • Josephs KS; Regional Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK.
  • McEntagart M; Medical Genetics, St George's University Hospitals, London, UK.
  • Lanpher B; Medical Genetics, St George's University Hospitals, London, UK.
  • Nickels KC; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.
  • Haworth A; Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
  • Reed L; Congenica, Wellcome Genome Campus, Cambridge, UK.
  • Cappuccio G; Congenica, Wellcome Genome Campus, Cambridge, UK.
  • Mammi I; Department of Translational Medicine, Federico II University of Naples, Naples, Italy.
  • Tarnowski JM; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
  • Novelli A; AULSS3 Serenissima, Ospedale Dolo, Dolo, Italy.
  • Melis D; Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCSS, Rome, Italy.
  • Callewaert B; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
  • Dallapiccola B; Dipartimento di Medicina, Chirurgia e Odontoiatria "Scuola Medica Salernitana", Università di Salerno, Salerno, Italy.
  • Klee E; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
  • Tartaglia M; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Clin Genet ; 98(2): 172-178, 2020 08.
Article en En | MEDLINE | ID: mdl-32415735
UBE2A deficiency, that is, intellectual disability (ID) Nascimento type (MIM 300860), is an X-linked syndrome characterized by developmental delay, moderate to severe ID, seizures, dysmorphisms, skin anomalies, and urogenital malformations. Forty affected subjects have been reported thus far, with 31 cases having intragenic UBE2A variants. Here, we report on additional eight affected subjects from seven unrelated families who were found to be hemizygous for previously unreported UBE2A missense variants (p.Glu62Lys, p.Arg95Cys, p.Thr99Ala, and p.Arg135Trp) or small in-frame deletions (p.Val81_Ala83del, and p.Asp101del). A wide phenotypic spectrum was documented in these subjects, ranging from moderate ID associated with mild dysmorphisms to severe features including congenital heart defects (CHD), severe cognitive impairment, and pineal gland tumors. Four variants affected residues (Glu62, Arg95, Thr99 and Asp101) that contribute to stabilizing the structure of the E3 binding domain. The three-residue in-frame deletion, p.Val81_Ala83del, resulted from aberrant processing of the transcript. This variant and p.Arg135Trp mapped to regions of the protein located far from the E3 binding region, and caused variably accelerated protein degradation. By reviewing available clinical information, we revise the clinical and molecular profile of the disorder and document genotype-phenotype correlations. Pineal gland cysts/tumors, CHD and hypogammaglobulinemia emerge as recurrent features.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Genéticas Ligadas al Cromosoma X / Enzimas Ubiquitina-Conjugadoras / Cardiopatías Congénitas / Discapacidad Intelectual Límite: Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Clin Genet Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Dinamarca
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Genéticas Ligadas al Cromosoma X / Enzimas Ubiquitina-Conjugadoras / Cardiopatías Congénitas / Discapacidad Intelectual Límite: Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Clin Genet Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Dinamarca