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Rare SUZ12 variants commonly cause an overgrowth phenotype.
Cyrus, Sharri S; Cohen, Ana S A; Agbahovbe, Ruky; Avela, Kristiina; Yeung, Kit S; Chung, Brian H Y; Luk, Ho-Ming; Tkachenko, Nataliya; Choufani, Sanaa; Weksberg, Rosanna; Lopez-Rangel, Elena; Brown, Kathleen; Saenz, Margarita S; Svihovec, Shayna; McCandless, Shawn E; Bird, Lynne M; Garcia, Aixa Gonzalez; Gambello, Michael J; McWalter, Kirsty; Schnur, Rhonda E; An, Jianghong; Jones, Steven J M; Bhalla, Sanjiv K; Pinz, Hailey; Braddock, Stephen R; Gibson, William T.
Afiliación
  • Cyrus SS; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
  • Cohen ASA; British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  • Agbahovbe R; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
  • Avela K; British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  • Yeung KS; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
  • Chung BHY; British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
  • Luk HM; Department of Clinical Genetics, Helsinki University Hospital, HUSLAB, Helsinki, Finland.
  • Tkachenko N; Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
  • Choufani S; Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
  • Weksberg R; Clinical Genetic Service, Department of Health, Hong Kong, Hong Kong.
  • Lopez-Rangel E; Medical Genetics Service, Medical Genetics Center Dr. Jacinto de Magalhães, Porto Hospital Center, Porto, Portugal.
  • Brown K; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Saenz MS; Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Svihovec S; Department of Pediatrics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • McCandless SE; Department of Medical Genetics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
  • Bird LM; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
  • Garcia AG; Section of Genetics and Metabolism, Department of Pediatrics, The Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • Gambello MJ; Section of Genetics and Metabolism, Department of Pediatrics, The Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • McWalter K; Section of Genetics and Metabolism, Department of Pediatrics, The Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • Schnur RE; Section of Genetics and Metabolism, Department of Pediatrics, The Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • An J; Department of Pediatrics, University of California, San Diego, California.
  • Jones SJM; Genetics/Dysmorphology, Rady Children's Hospital San Diego, San Diego, California.
  • Bhalla SK; Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
  • Pinz H; Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
  • Braddock SR; Clinical Genomics, GeneDx, Gaithersburg, Maryland.
  • Gibson WT; Clinical Genomics, GeneDx, Gaithersburg, Maryland.
Am J Med Genet C Semin Med Genet ; 181(4): 532-547, 2019 12.
Article en En | MEDLINE | ID: mdl-31736240
The Polycomb repressive complex 2 is an epigenetic writer and recruiter with a role in transcriptional silencing. Constitutional pathogenic variants in its component proteins have been found to cause two established overgrowth syndromes: Weaver syndrome (EZH2-related overgrowth) and Cohen-Gibson syndrome (EED-related overgrowth). Imagawa et al. (2017) initially reported a singleton female with a Weaver-like phenotype with a rare coding SUZ12 variant-the same group subsequently reported two additional affected patients. Here we describe a further 10 patients (from nine families) with rare heterozygous SUZ12 variants who present with a Weaver-like phenotype. We report four frameshift, two missense, one nonsense, and two splice site variants. The affected patients demonstrate variable pre- and postnatal overgrowth, dysmorphic features, musculoskeletal abnormalities and developmental delay/intellectual disability. Some patients have genitourinary and structural brain abnormalities, and there may be an association with respiratory issues. The addition of these 10 patients makes a compelling argument that rare pathogenic SUZ12 variants frequently cause overgrowth, physical abnormalities, and abnormal neurodevelopmental outcomes in the heterozygous state. Pathogenic SUZ12 variants may be de novo or inherited, and are sometimes inherited from a mildly-affected parent. Larger samples sizes will be needed to elucidate whether one or more clinically-recognizable syndromes emerge from different variant subtypes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Complejo Represivo Polycomb 2 / Trastornos del Crecimiento Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Am J Med Genet C Semin Med Genet Asunto de la revista: GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Canadá

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Complejo Represivo Polycomb 2 / Trastornos del Crecimiento Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Am J Med Genet C Semin Med Genet Asunto de la revista: GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Canadá
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