Skip to Content
Merck
  • Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.

Nature genetics (2021-07-03)
Margot A Cousin, Blake A Creighton, Keith A Breau, Rebecca C Spillmann, Erin Torti, Sruthi Dontu, Swarnendu Tripathi, Deepa Ajit, Reginald J Edwards, Simone Afriyie, Julia C Bay, Kathryn M Harper, Alvaro A Beltran, Lorena J Munoz, Liset Falcon Rodriguez, Michael C Stankewich, Richard E Person, Yue Si, Elizabeth A Normand, Amy Blevins, Alison S May, Louise Bier, Vimla Aggarwal, Grazia M S Mancini, Marjon A van Slegtenhorst, Kirsten Cremer, Jessica Becker, Hartmut Engels, Stefan Aretz, Jennifer J MacKenzie, Eva Brilstra, Koen L I van Gassen, Richard H van Jaarsveld, Renske Oegema, Gretchen M Parsons, Paul Mark, Ingo Helbig, Sarah E McKeown, Robert Stratton, Benjamin Cogne, Bertrand Isidor, Pilar Cacheiro, Damian Smedley, Helen V Firth, Tatjana Bierhals, Katja Kloth, Deike Weiss, Cecilia Fairley, Joseph T Shieh, Amy Kritzer, Parul Jayakar, Evangeline Kurtz-Nelson, Raphael A Bernier, Tianyun Wang, Evan E Eichler, Ingrid M B H van de Laar, Allyn McConkie-Rosell, Marie T McDonald, Jennifer Kemppainen, Brendan C Lanpher, Laura E Schultz-Rogers, Lauren B Gunderson, Pavel N Pichurin, Grace Yoon, Michael Zech, Robert Jech, Juliane Winkelmann, Adriana S Beltran, Michael T Zimmermann, Brenda Temple, Sheryl S Moy, Eric W Klee, Queenie K-G Tan, Damaris N Lorenzo
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Tubulin Antibody, beta III isoform, CT, clone TU-20 (Similar to TUJ1), ascites fluid, clone TU-20 (Similar to TUJ1), Chemicon®
Sigma-Aldrich
HRV-3C Protease, Biotin tagged, Recombinant protein, 0.8-1.2 mg/mL, aqueous solution