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Phenotypic and genotypic characterization of families with complex intellectual disability identified pathogenic genetic variations in known and novel disease genes.
Darvish, Hossein; Azcona, Luis J; Tafakhori, Abbas; Mesias, Roxana; Ahmadifard, Azadeh; Sanchez, Elena; Habibi, Arman; Alehabib, Elham; Johari, Amir Hossein; Emamalizadeh, Babak; Jamali, Faezeh; Chapi, Marjan; Jamshidi, Javad; Kajiwara, Yuji; Paisán-Ruiz, Coro.
Afiliación
  • Darvish H; Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran.
  • Azcona LJ; Department of Medical Genetics, Semnan University of Medical Sciences, Semnan, Iran.
  • Tafakhori A; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
  • Mesias R; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
  • Ahmadifard A; Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • Sanchez E; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
  • Habibi A; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
  • Alehabib E; Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Johari AH; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
  • Emamalizadeh B; Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • Jamali F; Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Chapi M; Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Jamshidi J; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Kajiwara Y; Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Paisán-Ruiz C; Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sci Rep ; 10(1): 968, 2020 01 22.
Article en En | MEDLINE | ID: mdl-31969655
Intellectual disability (ID), which presents itself during childhood, belongs to a group of neurodevelopmental disorders (NDDs) that are clinically widely heterogeneous and highly heritable, often being caused by single gene defects. Indeed, NDDs can be attributed to mutations at over 1000 loci, and all type of mutations, ranging from single nucleotide variations (SNVs) to large, complex copy number variations (CNVs), have been reported in patients with ID and other related NDDs. In this study, we recruited seven different recessive NDD families with comorbidities to perform a detailed clinical characterization and a complete genomic analysis that consisted of a combination of high throughput SNP-based genotyping and whole-genome sequencing (WGS). Different disease-associated loci and pathogenic gene mutations were identified in each family, including known (n = 4) and novel (n = 2) mutations in known genes (NAGLU, SLC5A2, POLR3B, VPS13A, SYN1, SPG11), and the identification of a novel disease gene (n = 1; NSL1). Functional analyses were additionally performed in a gene associated with autism-like symptoms and epileptic seizures for further proof of pathogenicity. Lastly, detailed genotype-phenotype correlations were carried out to assist with the diagnosis of prospective families and to determine genomic variation with clinical relevance. We concluded that the combination of linkage analyses and WGS to search for disease genes still remains a fruitful strategy for complex diseases with a variety of mutated genes and heterogeneous phenotypic manifestations, allowing for the identification of novel mutations, genes, and phenotypes, and leading to improvements in both diagnostic strategies and functional characterization of disease mechanisms.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Variación Genética / Genotipo / Discapacidad Intelectual Límite: Female / Humans / Male Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Variación Genética / Genotipo / Discapacidad Intelectual Límite: Female / Humans / Male Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Reino Unido