TY - JOUR
T1 - SPTBN5, Encoding the βV-Spectrin Protein, Leads to a Syndrome of Intellectual Disability, Developmental Delay, and Seizures
AU - Khan, Amjad
AU - Bruno, Lucia Pia
AU - Alomar, Fadhel
AU - Umair, Muhammad
AU - Pinto, Anna Maria
AU - Khan, Abid Ali
AU - Khan, Alamzeb
AU - Saima,
AU - Fabbiani, Alessandra
AU - Zguro, Kristina
AU - Furini, Simone
AU - Mencarelli, Maria Antonietta
AU - Renieri, Alessandra
AU - Resciniti, Sara
AU - Peña-Guerra, Karla A.
AU - Guzmán-Vega, Francisco J.
AU - Arold, Stefan T.
AU - Ariani, Francesca
AU - Khan, Shahid Niaz
N1 - 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.
PY - 2022/6/17
Y1 - 2022/6/17
N2 - 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.
AB - 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.
KW - heterozygous mutation
KW - intellectual disability (ID)
KW - protein modeling 3
KW - SPTBN5
KW - whole exome sequencing (WES)
UR - http://www.scopus.com/inward/record.url?scp=85133641711&partnerID=8YFLogxK
U2 - 10.3389/fnmol.2022.877258
DO - 10.3389/fnmol.2022.877258
M3 - Article
C2 - 35782384
AN - SCOPUS:85133641711
SN - 1662-5099
VL - 15
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 877258
ER -