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A novel in-frame deletion affecting the BAR domain of OPHN1 in a family with intellectual disability and hippocampal alterations.
Santos-Rebouças, Cíntia Barros; Belet, Stefanie; Guedes de Almeida, Luciana; Ribeiro, Márcia Gonçalves; Medina-Acosta, Enrique; Bahia, Paulo Roberto Valle; Alves da Silva, Antônio Francisco; Lima dos Santos, Flávia; Borges de Lacerda, Glenda Corrêa; Pimentel, Márcia Mattos Gonçalves; Froyen, Guy.
Afiliación
  • Santos-Rebouças CB; Department of Genetics, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Belet S; 1] Human Genome Laboratory, VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium [2] Human Genome Laboratory, Center for Human, Genetics, KU Leuven, Leuven, Belgium.
  • Guedes de Almeida L; Department of Genetics, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Ribeiro MG; Clinical Genetics Service, IPPMG, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Medina-Acosta E; Laboratory of Biotechnology, Center for Biosciences and Biotechnology, State University of North Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil.
  • Bahia PR; Department of Neurology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Alves da Silva AF; Laboratory of Biotechnology, Center for Biosciences and Biotechnology, State University of North Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil.
  • Lima dos Santos F; Department of Genetics, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Borges de Lacerda GC; 1] Epilepsy Outpatient Section, Fluminense Federal University, Rio de Janeiro, Brazil [2] Neurology and Neurophysiology Service, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Pimentel MM; Department of Genetics, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Froyen G; 1] Human Genome Laboratory, VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium [2] Human Genome Laboratory, Center for Human, Genetics, KU Leuven, Leuven, Belgium.
Eur J Hum Genet ; 22(5): 644-51, 2014 May.
Article en En | MEDLINE | ID: mdl-24105372
Oligophrenin-1 (OPHN1) is one of at least seven genes located on chromosome X that take part in Rho GTPase-dependent signaling pathways involved in X-linked intellectual disability (XLID). Mutations in OPHN1 were primarily described as an exclusive cause of non-syndromic XLID, but the re-evaluation of the affected individuals using brain imaging displayed fronto-temporal atrophy and cerebellar hypoplasia as neuroanatomical marks. In this study, we describe clinical, genetic and neuroimaging data of a three generation Brazilian XLID family co-segregating a novel intragenic deletion in OPHN1. This deletion results in an in-frame loss of exon 7 at transcription level (c.781_891del; r.487_597del), which is predicted to abolish 37 amino acids from the highly conserved N-terminal BAR domain of OPHN1. cDNA expression analysis demonstrated that the mutant OPHN1 transcript is stable and no abnormal splicing was observed. Features shared by the affected males of this family include neonatal hypotonia, strabismus, prominent root of the nose, deep set eyes, hyperactivity and instability/intolerance to frustration. Cranial MRI scans showed large lateral ventricles, vermis hypoplasia and cystic dilatation of the cisterna magna in all affected males. Interestingly, hippocampal alterations that have not been reported in patients with loss-of-function OPHN1 mutations were found in three affected individuals, suggesting an important function for the BAR domain in the hippocampus. This is the first description of an in-frame deletion within the BAR domain of OPHN1 and could provide new insights into the role of this domain in relation to brain and cognitive development or function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Nucleares / Sistemas de Lectura / Eliminación de Secuencia / Proteínas Activadoras de GTPasa / Proteínas del Citoesqueleto / Dominios y Motivos de Interacción de Proteínas / Hipocampo / Discapacidad Intelectual Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adolescent / Adult / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2014 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Nucleares / Sistemas de Lectura / Eliminación de Secuencia / Proteínas Activadoras de GTPasa / Proteínas del Citoesqueleto / Dominios y Motivos de Interacción de Proteínas / Hipocampo / Discapacidad Intelectual Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adolescent / Adult / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2014 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido