ArticleAmerican journal of human genetics2010
Dominant-negative mutations in alpha-II spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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68 citing papers in PubMed, 152 citations in OpenAlex.
- When the Cytoskeleton Fails: Primary Structural Defects Underlying Disorders with Neurological Involvement.International journal of molecular sciences · 2026Review
- Pathophysiological Mechanisms Fostering Developmental and Epileptic Encephalopathies (DEE): a Complex Interplay between Genetics, Inflammation and Neurodegeneration.Current neurology and neuroscience reports · 2025Review
- Review
- CELF2 Deficiency Demonstrates Autism-Like Behaviors and Interferes with Late Development of Cortical Neurons in Mice.Molecular neurobiology · 2025Article
- Critical role of alpha spectrin in DNA repair: the importance of μ-calpain and Fanconi anemia proteins.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- A De Novo Splicing Mutation ofInternational journal of molecular sciences · 2024Article
- Review
- Spectrins: molecular organizers and targets of neurological disorders.Nature reviews. Neuroscience · 2023Review
- Progressive Ataxia, Memory Impairments, and Seizure Episodes inBrain sciences · 2023Article
- De Novo and Dominantly Inherited SPTAN1 Mutations Cause Spastic Paraplegia and Cerebellar Ataxia.Movement disorders : official journal of the Movement Disorder Society · 2022Article
- SPTAN1 variants likely cause autosomal recessive complicated hereditary spastic paraplegia.Journal of human genetics · 2022Article
- Longitudinal neurodevelopmental profile of a pediatric patient with de novo SPTAN1, epilepsy, and left hippocampal sclerosis.Epilepsy & behavior reports · 2022Article
- Pathophysiological Roles of Abnormal Axon Initial Segments in Neurodevelopmental Disorders.Cells · 2021Review
- Heterozygous variants in SPTBN1 cause intellectual disability and autism.American journal of medical genetics. Part A · 2021Article
- Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.Nature genetics · 2021Article
- Age-dependent ataxia and neurodegeneration caused by an αII spectrin mutation with impaired regulation of its calpain sensitivity.Scientific reports · 2021Article
- The Spread of Spectrin in Ataxia and Neurodegenerative Disease.Journal of experimental neurology · 2021Article
- A Fresh Look at the Structure, Regulation, and Functions of Fodrin.Molecular and cellular biology · 2020Review
- Cargo hold and delivery: Ankyrins, spectrins, and their functional patterning of neurons.Cytoskeleton (Hoboken, N.J.) · 2020Review
- A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis.NPJ genomic medicine · 2020Article
8 more citing papers are in PubMed but not listed here.
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27 authors at 14 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
A de novo 9q33.3-q34.11 microdeletion involving STXBP1 has been found in one of four individuals (group A) with early-onset West syndrome, severe hypomyelination, poor visual attention, and developmental delay. Although haploinsufficiency of STXBP1 was involved in early infantile epileptic encephalopathy in a previous different cohort study (group B), no mutations of STXBP1 were found in two of the remaining three subjects of group A (one was unavailable). We assumed that another gene within the deletion might contribute to the phenotype of group A. SPTAN1 encoding alpha-II spectrin, which is essential for proper myelination in zebrafish, turned out to be deleted. In two subjects, an in-frame 3 bp deletion and a 6 bp duplication in SPTAN1 were found at the initial nucleation site of the alpha/beta spectrin heterodimer. SPTAN1 was further screened in six unrelated individuals with WS and hypomyelination, but no mutations were found. Recombinant mutant (mut) and wild-type (WT) alpha-II spectrin could assemble heterodimers with beta-II spectrin, but alpha-II (mut)/beta-II spectrin heterodimers were thermolabile compared with the alpha-II (WT)/beta-II heterodimers. Transient expression in mouse cortical neurons revealed aggregation of alpha-II (mut)/beta-II and alpha-II (mut)/beta-III spectrin heterodimers, which was also observed in lymphoblastoid cells from two subjects with in-frame mutations. Clustering of ankyrinG and voltage-gated sodium channels at axon initial segment (AIS) was disturbed in relation to the aggregates, together with an elevated action potential threshold. These findings suggest that pathological aggregation of alpha/beta spectrin heterodimers and abnormal AIS integrity resulting from SPTAN1 mutations were involved in pathogenesis of infantile epilepsy.
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