SPTBN5, Encoding the βV-Spectrin Protein, Leads to a Syndrome of Intellectual Disability, Developmental Delay, and Seizures

Amjad Khan*, Lucia Pia Bruno, Fadhel Alomar, Muhammad Umair, Anna Maria Pinto, Abid Ali Khan, Alamzeb Khan, Saima, Alessandra Fabbiani, Kristina Zguro, Simone Furini, Maria Antonietta Mencarelli, Alessandra Renieri, Sara Resciniti, Karla A. Peña-Guerra, Francisco J. Guzmán-Vega, Stefan T. Arold, Francesca Ariani, Shahid Niaz Khan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Article number877258
JournalFrontiers in Molecular Neuroscience
StatePublished - Jun 17 2022

Bibliographical note

Funding Information:
This research by KP-G, FG-V, and SA were supported by the King Abdullah University of Science and Technology (KAUST) through the baseline fund and the Award No. FCC/1/1976-25 and REI/1/4446-01 from the Office of Sponsored Research (OSR). For computer time, this research used the resources of the Supercomputing Laboratory at KAUST. We are grateful to our patients for their cooperation. This work was generated within the ERN ITHACA (European Reference Network for Intellectual Disability, Telehealth, Autism, and Congenital Anomalies). The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation, and other genetic diseases, member of the Telethon Network of Genetic Biobanks (project nos. GTB12001 and GFB18001), funded by Telethon Italy, and of the EuroBioBank network provided us with specimens.

Publisher Copyright:
Copyright © 2022 Khan, Bruno, Alomar, Umair, Pinto, Khan, Khan, Saima, Fabbiani, Zguro, Furini, Mencarelli, Renieri, Resciniti, Peña-Guerra, Guzmán-Vega, Arold, Ariani and Khan.


  • heterozygous mutation
  • intellectual disability (ID)
  • protein modeling 3
  • SPTBN5
  • whole exome sequencing (WES)

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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