Frontiers in Molecular Neuroscience (Jun 2022)
SPTBN5, Encoding the βV-Spectrin Protein, Leads to a Syndrome of Intellectual Disability, Developmental Delay, and Seizures
- Amjad Khan,
- Amjad Khan,
- Lucia Pia Bruno,
- Lucia Pia Bruno,
- Fadhel Alomar,
- Muhammad Umair,
- Muhammad Umair,
- Anna Maria Pinto,
- Abid Ali Khan,
- Alamzeb Khan,
- Saima,
- Alessandra Fabbiani,
- Alessandra Fabbiani,
- Kristina Zguro,
- Simone Furini,
- Maria Antonietta Mencarelli,
- Alessandra Renieri,
- Alessandra Renieri,
- Alessandra Renieri,
- Sara Resciniti,
- Sara Resciniti,
- Karla A. Peña-Guerra,
- Francisco J. Guzmán-Vega,
- Stefan T. Arold,
- Stefan T. Arold,
- Francesca Ariani,
- Francesca Ariani,
- Francesca Ariani,
- Shahid Niaz Khan
Affiliations
- Amjad Khan
- Faculty of Science, Department of Biological Sciences (Zoology), University of Lakki Marwat, Lakki Marwat, Pakistan
- Amjad Khan
- Medical Genetics, University of Siena, Siena, Italy
- Lucia Pia Bruno
- Medical Genetics, University of Siena, Siena, Italy
- Lucia Pia Bruno
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Fadhel Alomar
- Department of Pharmacology and Toxicology, College of Clinical Pharmacy, Imam Abdulrahman, Bin Faisal University, Dammam, Saudi Arabia
- Muhammad Umair
- Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
- Muhammad Umair
- Department of Life Sciences, School of Science, University of Management and Technology (UMT), Lahore, Pakistan
- Anna Maria Pinto
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Abid Ali Khan
- Faculty of Science, Department of Chemical Sciences, University of Lakki Marwat, Lakki Marwat, Pakistan
- Alamzeb Khan
- Department of Pediatrics, Yale School of Medicine, Yal University, New Heaven, CT, United States
- Saima
- 0Department of Biotechnology, Abdul Wali Khan University Mardan, Mardan, Pakistan
- Alessandra Fabbiani
- Medical Genetics, University of Siena, Siena, Italy
- Alessandra Fabbiani
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Kristina Zguro
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Simone Furini
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Maria Antonietta Mencarelli
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Alessandra Renieri
- Medical Genetics, University of Siena, Siena, Italy
- Alessandra Renieri
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Alessandra Renieri
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Sara Resciniti
- Medical Genetics, University of Siena, Siena, Italy
- Sara Resciniti
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Karla A. Peña-Guerra
- 1Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
- Francisco J. Guzmán-Vega
- 1Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
- Stefan T. Arold
- 1Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
- Stefan T. Arold
- 2Centre de Biologie Structurale (CBS), INSERM, CNRS, Université de Montpellier, Montpellier, France
- Francesca Ariani
- Medical Genetics, University of Siena, Siena, Italy
- Francesca Ariani
- Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Francesca Ariani
- Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
- Shahid Niaz Khan
- 3Department of Zoology, Kohat University of Science and Technology, Kohat, Pakistan
- DOI
- https://doi.org/10.3389/fnmol.2022.877258
- Journal volume & issue
-
Vol. 15
Abstract
Whole exome sequencing has provided significant opportunities to discover novel candidate genes for intellectual disability and autism spectrum disorders. Variants in the spectrin genes SPTAN1, SPTBN1, SPTBN2, and SPTBN4 have been associated with neurological disorders; however, SPTBN5 gene-variants have not been associated with any human disorder. This is the first report that associates SPTBN5 gene variants (ENSG00000137877: c.266A>C; p.His89Pro, c.9784G>A; p.Glu3262Lys, c.933C>G; p.Tyr311Ter, and c.8809A>T; p.Asn2937Tyr) causing neurodevelopmental phenotypes in four different families. The SPTBN5-associated clinical traits in our patients include intellectual disability (mild to severe), aggressive tendencies, accompanied by variable features such as craniofacial and physical dysmorphisms, autistic behavior, and gastroesophageal reflux. We also provide a review of the existing literature related to other spectrin genes, which highlights clinical features partially overlapping with SPTBN5.
Keywords
- intellectual disability (ID)
- whole exome sequencing (WES)
- SPTBN5
- heterozygous mutation
- protein modeling 3
