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

doi:10.3389/fnmol.2022.877258

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 journal › Article › peer-review

10 Scopus citations

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.

Original language	English (US)
Article number	877258
Journal	Frontiers in Molecular Neuroscience
Volume	15
DOIs	https://doi.org/10.3389/fnmol.2022.877258
State	Published - 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.

Keywords

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

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience

Access to Document

10.3389/fnmol.2022.877258

Cite this

Khan, A., Bruno, L. P., Alomar, F., Umair, M., Pinto, A. M., Khan, A. A., Khan, A., Saima, Fabbiani, A., Zguro, K., Furini, S., Mencarelli, M. A., Renieri, A., Resciniti, S., Peña-Guerra, K. A., Guzmán-Vega, F. J., Arold, S. T., Ariani, F., & Khan, S. N. (2022). SPTBN5, Encoding the βV-Spectrin Protein, Leads to a Syndrome of Intellectual Disability, Developmental Delay, and Seizures. Frontiers in Molecular Neuroscience, 15, Article 877258. https://doi.org/10.3389/fnmol.2022.877258

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

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 = "heterozygous mutation, intellectual disability (ID), protein modeling 3, SPTBN5, whole exome sequencing (WES)",

author = "Amjad Khan and Bruno, {Lucia Pia} and Fadhel Alomar and Muhammad Umair and Pinto, {Anna Maria} and Khan, {Abid Ali} and Alamzeb Khan and Saima and Alessandra Fabbiani and Kristina Zguro and Simone Furini and Mencarelli, {Maria Antonietta} and Alessandra Renieri and Sara Resciniti and Pe{\~n}a-Guerra, {Karla A.} and Guzm{\'a}n-Vega, {Francisco J.} and Arold, {Stefan T.} and Francesca Ariani and Khan, {Shahid Niaz}",

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 {\textcopyright} 2022 Khan, Bruno, Alomar, Umair, Pinto, Khan, Khan, Saima, Fabbiani, Zguro, Furini, Mencarelli, Renieri, Resciniti, Pe{\~n}a-Guerra, Guzm{\'a}n-Vega, Arold, Ariani and Khan.",

year = "2022",

month = jun,

day = "17",

doi = "10.3389/fnmol.2022.877258",

language = "English (US)",

volume = "15",

journal = "Frontiers in Molecular Neuroscience",

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publisher = "Frontiers Media S.A.",

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Khan, A, Bruno, LP, Alomar, F, Umair, M, Pinto, AM, Khan, AA, Khan, A, Saima, Fabbiani, A, Zguro, K, Furini, S, Mencarelli, MA, Renieri, A, Resciniti, S, Peña-Guerra, KA , Guzmán-Vega, FJ , Arold, ST, Ariani, F & Khan, SN 2022, 'SPTBN5, Encoding the βV-Spectrin Protein, Leads to a Syndrome of Intellectual Disability, Developmental Delay, and Seizures', Frontiers in Molecular Neuroscience, vol. 15, 877258. https://doi.org/10.3389/fnmol.2022.877258

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)

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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 -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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