小柯机器人

美国北卡罗来纳大学Damaris N. Lorenzo、Margot A. Cousin等研究人员合作发现，致病性SPTBN1变异导致常染色体显性遗传神经发育综合征。2021年7月1日，《自然—遗传学》杂志在线发表了这项成果。

研究人员在29名个体中鉴定了杂合的SPTBN1变异，这些个体出现：发育、语言和运动发育迟缓；轻度至重度智力障碍；自闭症特征；癫痫发作;行为和运动异常；张力减退；以及可变的畸形面部特征。研究人员表明，这些SPTBN1变体会影响βII-血影蛋白稳定性、破坏与关键分子伴侣的结合并扰乱细胞骨架组织和动态。这项研究将SPTBN1变异体定义为神经发育综合征的遗传基础，扩大了影响大脑的血影蛋白病集，并强调了βII-血影蛋白在中枢神经系统中的关键作用。

据了解，SPTBN1编码 βII-血影蛋白，这是一种普遍表达的β-血影蛋白，形成与质膜相关的微米级网络。缺乏神经元βII-血影蛋白的小鼠在皮质组织、发育迟缓和行为缺陷方面存在缺陷。这些表型虽然不太严重，但在单倍体不足的动物中观察到，这表明携带杂合SPTBN1变体的个体也可能表现出可测量的神经发育和功能损害。

附：英文原文

Title: Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

Author: 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

Issue&Volume: 2021-07-01

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.

DOI: 10.1038/s41588-021-00886-z

Source: https://www.nature.com/articles/s41588-021-00886-z

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex