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Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

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Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome. / Cousin, Margot A; Creighton, Blake A; Breau, Keith A; Spillmann, Rebecca C; Torti, Erin; Dontu, Sruthi; Tripathi, Swarnendu; Ajit, Deepa; Edwards, Reginald J; Afriyie, Simone; Bay, Julia C; Harper, Kathryn M; Beltran, Alvaro A; Munoz, Lorena J; Falcon Rodriguez, Liset; Stankewich, Michael C; Person, Richard E; Si, Yue; Normand, Elizabeth A; Blevins, Amy; May, Alison S; Bier, Louise; Aggarwal, Vimla; Mancini, Grazia M S; van Slegtenhorst, Marjon A; Cremer, Kirsten; Becker, Jessica; Engels, Hartmut; Aretz, Stefan; MacKenzie, Jennifer J; Brilstra, Eva; van Gassen, Koen L I; van Jaarsveld, Richard H; Oegema, Renske; Parsons, Gretchen M; Mark, Paul; Helbig, Ingo; McKeown, Sarah E; Stratton, Robert; Cogne, Benjamin; Isidor, Bertrand; Cacheiro, Pilar; Smedley, Damian; Firth, Helen V; Bierhals, Tatjana; Kloth, Katja; Weiss, Deike; Fairley, Cecilia; Shieh, Joseph T; Kritzer, Amy; Jayakar, Parul; Kurtz-Nelson, Evangeline; Bernier, Raphael A; Wang, Tianyun; Eichler, Evan E; van de Laar, Ingrid M B H; McConkie-Rosell, Allyn; McDonald, Marie T; Kemppainen, Jennifer; Lanpher, Brendan C; Schultz-Rogers, Laura E; Gunderson, Lauren B; Pichurin, Pavel N; Yoon, Grace; Zech, Michael; Jech, Robert; Winkelmann, Juliane; Beltran, Adriana S; Zimmermann, Michael T; Temple, Brenda; Moy, Sheryl S; Klee, Eric W; Tan, Queenie K-G; Lorenzo, Damaris N; Undiagnosed Diseases Network.

in: NAT GENET, Jahrgang 53, Nr. 7, 07.2021, S. 1006-1021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Cousin, MA, Creighton, BA, Breau, KA, Spillmann, RC, Torti, E, Dontu, S, Tripathi, S, Ajit, D, Edwards, RJ, Afriyie, S, Bay, JC, Harper, KM, Beltran, AA, Munoz, LJ, Falcon Rodriguez, L, Stankewich, MC, Person, RE, Si, Y, Normand, EA, Blevins, A, May, AS, Bier, L, Aggarwal, V, Mancini, GMS, van Slegtenhorst, MA, Cremer, K, Becker, J, Engels, H, Aretz, S, MacKenzie, JJ, Brilstra, E, van Gassen, KLI, van Jaarsveld, RH, Oegema, R, Parsons, GM, Mark, P, Helbig, I, McKeown, SE, Stratton, R, Cogne, B, Isidor, B, Cacheiro, P, Smedley, D, Firth, HV, Bierhals, T, Kloth, K, Weiss, D, Fairley, C, Shieh, JT, Kritzer, A, Jayakar, P, Kurtz-Nelson, E, Bernier, RA, Wang, T, Eichler, EE, van de Laar, IMBH, McConkie-Rosell, A, McDonald, MT, Kemppainen, J, Lanpher, BC, Schultz-Rogers, LE, Gunderson, LB, Pichurin, PN, Yoon, G, Zech, M, Jech, R, Winkelmann, J, Beltran, AS, Zimmermann, MT, Temple, B, Moy, SS, Klee, EW, Tan, QK-G, Lorenzo, DN & Undiagnosed Diseases Network 2021, 'Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome', NAT GENET, Jg. 53, Nr. 7, S. 1006-1021. https://doi.org/10.1038/s41588-021-00886-z

APA

Cousin, M. A., Creighton, B. A., Breau, K. A., Spillmann, R. C., Torti, E., Dontu, S., Tripathi, S., Ajit, D., Edwards, R. J., Afriyie, S., Bay, J. C., Harper, K. M., Beltran, A. A., Munoz, L. J., Falcon Rodriguez, L., Stankewich, M. C., Person, R. E., Si, Y., Normand, E. A., ... Undiagnosed Diseases Network (2021). Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome. NAT GENET, 53(7), 1006-1021. https://doi.org/10.1038/s41588-021-00886-z

Vancouver

Cousin MA, Creighton BA, Breau KA, Spillmann RC, Torti E, Dontu S et al. Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome. NAT GENET. 2021 Jul;53(7):1006-1021. https://doi.org/10.1038/s41588-021-00886-z

Bibtex

@article{9fabfbffd6144afe880df4f899ccad0e,
title = "Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome",
abstract = "SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system.",
keywords = "Animals, Genes, Dominant, Genetic Association Studies/methods, Genetic Predisposition to Disease, Genetic Variation, Heterozygote, Humans, Mice, Neurodevelopmental Disorders/diagnosis, Phenotype, Spectrin/genetics",
author = "Cousin, {Margot A} and Creighton, {Blake A} and Breau, {Keith A} and Spillmann, {Rebecca C} and Erin Torti and Sruthi Dontu and Swarnendu Tripathi and Deepa Ajit and Edwards, {Reginald J} and Simone Afriyie and Bay, {Julia C} and Harper, {Kathryn M} and Beltran, {Alvaro A} and Munoz, {Lorena J} and {Falcon Rodriguez}, Liset and Stankewich, {Michael C} and Person, {Richard E} and Yue Si and Normand, {Elizabeth A} and Amy Blevins and May, {Alison S} and Louise Bier and Vimla Aggarwal and Mancini, {Grazia M S} and {van Slegtenhorst}, {Marjon A} and Kirsten Cremer and Jessica Becker and Hartmut Engels and Stefan Aretz and MacKenzie, {Jennifer J} and Eva Brilstra and {van Gassen}, {Koen L I} and {van Jaarsveld}, {Richard H} and Renske Oegema and Parsons, {Gretchen M} and Paul Mark and Ingo Helbig and McKeown, {Sarah E} and Robert Stratton and Benjamin Cogne and Bertrand Isidor and Pilar Cacheiro and Damian Smedley and Firth, {Helen V} and Tatjana Bierhals and Katja Kloth and Deike Weiss and Cecilia Fairley and Shieh, {Joseph T} and Amy Kritzer and Parul Jayakar and Evangeline Kurtz-Nelson and Bernier, {Raphael A} and Tianyun Wang and Eichler, {Evan E} and {van de Laar}, {Ingrid M B H} and Allyn McConkie-Rosell and McDonald, {Marie T} and Jennifer Kemppainen and Lanpher, {Brendan C} and Schultz-Rogers, {Laura E} and Gunderson, {Lauren B} and Pichurin, {Pavel N} and Grace Yoon and Michael Zech and Robert Jech and Juliane Winkelmann and Beltran, {Adriana S} and Zimmermann, {Michael T} and Brenda Temple and Moy, {Sheryl S} and Klee, {Eric W} and Tan, {Queenie K-G} and Lorenzo, {Damaris N} and {Undiagnosed Diseases Network}",
note = "{\textcopyright} 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = jul,
doi = "10.1038/s41588-021-00886-z",
language = "English",
volume = "53",
pages = "1006--1021",
journal = "NAT GENET",
issn = "1061-4036",
publisher = "NATURE PUBLISHING GROUP",
number = "7",

}

RIS

TY - JOUR

T1 - Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

AU - Cousin, Margot A

AU - Creighton, Blake A

AU - Breau, Keith A

AU - Spillmann, Rebecca C

AU - Torti, Erin

AU - Dontu, Sruthi

AU - Tripathi, Swarnendu

AU - Ajit, Deepa

AU - Edwards, Reginald J

AU - Afriyie, Simone

AU - Bay, Julia C

AU - Harper, Kathryn M

AU - Beltran, Alvaro A

AU - Munoz, Lorena J

AU - Falcon Rodriguez, Liset

AU - Stankewich, Michael C

AU - Person, Richard E

AU - Si, Yue

AU - Normand, Elizabeth A

AU - Blevins, Amy

AU - May, Alison S

AU - Bier, Louise

AU - Aggarwal, Vimla

AU - Mancini, Grazia M S

AU - van Slegtenhorst, Marjon A

AU - Cremer, Kirsten

AU - Becker, Jessica

AU - Engels, Hartmut

AU - Aretz, Stefan

AU - MacKenzie, Jennifer J

AU - Brilstra, Eva

AU - van Gassen, Koen L I

AU - van Jaarsveld, Richard H

AU - Oegema, Renske

AU - Parsons, Gretchen M

AU - Mark, Paul

AU - Helbig, Ingo

AU - McKeown, Sarah E

AU - Stratton, Robert

AU - Cogne, Benjamin

AU - Isidor, Bertrand

AU - Cacheiro, Pilar

AU - Smedley, Damian

AU - Firth, Helen V

AU - Bierhals, Tatjana

AU - Kloth, Katja

AU - Weiss, Deike

AU - Fairley, Cecilia

AU - Shieh, Joseph T

AU - Kritzer, Amy

AU - Jayakar, Parul

AU - Kurtz-Nelson, Evangeline

AU - Bernier, Raphael A

AU - Wang, Tianyun

AU - Eichler, Evan E

AU - van de Laar, Ingrid M B H

AU - McConkie-Rosell, Allyn

AU - McDonald, Marie T

AU - Kemppainen, Jennifer

AU - Lanpher, Brendan C

AU - Schultz-Rogers, Laura E

AU - Gunderson, Lauren B

AU - Pichurin, Pavel N

AU - Yoon, Grace

AU - Zech, Michael

AU - Jech, Robert

AU - Winkelmann, Juliane

AU - Beltran, Adriana S

AU - Zimmermann, Michael T

AU - Temple, Brenda

AU - Moy, Sheryl S

AU - Klee, Eric W

AU - Tan, Queenie K-G

AU - Lorenzo, Damaris N

AU - Undiagnosed Diseases Network

N1 - © 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2021/7

Y1 - 2021/7

N2 - SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system.

AB - SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system.

KW - Animals

KW - Genes, Dominant

KW - Genetic Association Studies/methods

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Heterozygote

KW - Humans

KW - Mice

KW - Neurodevelopmental Disorders/diagnosis

KW - Phenotype

KW - Spectrin/genetics

U2 - 10.1038/s41588-021-00886-z

DO - 10.1038/s41588-021-00886-z

M3 - SCORING: Journal article

C2 - 34211179

VL - 53

SP - 1006

EP - 1021

JO - NAT GENET

JF - NAT GENET

SN - 1061-4036

IS - 7

ER -