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Homozygous Mutations in TBC1D23 Lead to a Non-degenerative Form of Pontocerebellar Hypoplasia.
Marin-Valencia, Isaac; Gerondopoulos, Andreas; Zaki, Maha S; Ben-Omran, Tawfeg; Almureikhi, Mariam; Demir, Ercan; Guemez-Gamboa, Alicia; Gregor, Anne; Issa, Mahmoud Y; Appelhof, Bart; Roosing, Susanne; Musaev, Damir; Rosti, Basak; Wirth, Sara; Stanley, Valentina; Baas, Frank; Barr, Francis A; Gleeson, Joseph G.
Afiliación
  • Marin-Valencia I; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Gerondopoulos A; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
  • Zaki MS; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, 12311 Cairo, Egypt.
  • Ben-Omran T; Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, 3050 Doha, Qatar.
  • Almureikhi M; Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, 3050 Doha, Qatar.
  • Demir E; Gazi University, Department of Pediatric Neurology, 06500 Ankara, Turkey.
  • Guemez-Gamboa A; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Gregor A; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Issa MY; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, 12311 Cairo, Egypt.
  • Appelhof B; Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Roosing S; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Musaev D; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Rady Children's Institute for Genomic Medicine, University of California, San Diego, San Diego, CA 92093, USA.
  • Rosti B; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Rady Children's Institute for Genomic Medicine, University of California, San Diego, San Diego, CA 92
  • Wirth S; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Rady Children's Institute for Genomic Medicine, University of California, San Diego, San Diego, CA 92093, USA.
  • Stanley V; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Rady Children's Institute for Genomic Medicine, University of California, San Diego, San Diego, CA 92093, USA.
  • Baas F; Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Barr FA; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
  • Gleeson JG; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA; Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Rady Children's Institute for Genomic Medicine, University of California, San Diego, San Diego, CA 92
Am J Hum Genet ; 101(3): 441-450, 2017 Sep 07.
Article en En | MEDLINE | ID: mdl-28823706
Pontocerebellar hypoplasia (PCH) represents a group of recessive developmental disorders characterized by impaired growth of the pons and cerebellum, which frequently follows a degenerative course. Currently, there are 10 partially overlapping clinical subtypes and 13 genes known mutated in PCH. Here, we report biallelic TBC1D23 mutations in six individuals from four unrelated families manifesting a non-degenerative form of PCH. In addition to reduced volume of pons and cerebellum, affected individuals had microcephaly, psychomotor delay, and ataxia. In zebrafish, tbc1d23 morphants replicated the human phenotype showing hindbrain volume loss. TBC1D23 localized at the trans-Golgi and was regulated by the small GTPases Arl1 and Arl8, suggesting a role in trans-Golgi membrane trafficking. Altogether, this study provides a causative link between TBC1D23 mutations and PCH and suggests a less severe clinical course than other PCH subtypes.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Cerebelosas / Proteínas Activadoras de GTPasa / Homocigoto / Microcefalia / Mutación Límite: Adolescent / Animals / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Am J Hum Genet Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Cerebelosas / Proteínas Activadoras de GTPasa / Homocigoto / Microcefalia / Mutación Límite: Adolescent / Animals / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Am J Hum Genet Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos