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Results for “SPTAN1”

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3 recordsLinked to original sources
PubMed2025

SPTAN1-Results of a Caregiver Survey.

Background: SPTAN1 variants are thought to affect the scaffolding that protects the axonal segment of neurons as well as neuronal synapses. The SPTAN1 gene is located in the 9q34.11 genomic region and encodes the cytoskeletal protein alpha II spectrin. Epilepsy, encephalopathy, and motor neuropathy are most commonly associated with SPTAN1 variants. Methods: An informed consent and questionnaire were developed in order to gather information from caregivers regarding their family members' SPTAN1 variant. Survey results are summarized descriptively, in order of frequency. Results: The results of a questionnaire filled out by the caregivers of loved ones who have a SPTAN1 mutation are summarized for 25 individuals, 14 males and 11 females, who have the SPTAN1 mutation. Conclusions: The results of this survey mirror those reported by other authors and include epilepsy, intellectual and motor delays, encephalopathy, and motor neuropathy. Additional effects of the SPTAN1 mutation reported here include absent or difficult speech, happy personality, decline in cognitive and motor skills with age, vision and hearing abnormalities, organ and skeletal effects, autoimmune diseases, and weakened immune systems.

Humans↗
PubMed2025

Heterozygous loss-of-function variants in SPTAN1 cause an early childhood onset distal myopathy.

PURPOSE: Heterozygous pathogenic variants in SPTAN1 cause a diverse spectrum of neurogenetic disorders ranging from peripheral and central nervous system involvement to complex syndromic presentations. We set out to investigate the role of SPTAN1 in genetically unsolved hereditary myopathies. METHODS: Through international collaboration we identified 14 families with distal weakness and heterozygous SPTAN1 loss-of-function variants. Clinical data, electrophysiology, muscle computed tomography or magnetic resonance imaging, and muscle biopsy findings were collected and standardized. SPTAN1 protein, messenger RNA expression analysis and copy DNA sequencing was performed on muscle tissue from 2 participants. RESULTS: Five families showed autosomal dominant mode of inheritance, whereas in 9 patients the variant was shown to be de novo, including 2 pairs of monozygotic twins. In 2 families, further segregation analysis was not possible. All affected participants presented with early childhood-onset distal weakness and foot abnormalities. Muscle magnetic resonance imaging or computed tomography in 10 patients showed fatty infiltration of the distal lower limb anterior compartment and/or selective involvement of the extensor hallucis longus muscle. Muscle biopsy revealed myopathic changes in 7 patients. Finally, we provide proof for nonsense-mediated decay in muscle tissue derived from 2 patients. CONCLUSION: We present evidence linking heterozygous SPTAN1 loss-of-function variants to childhood-onset distal myopathy in 14 unrelated families.

Humans↗
PubMed2026

Elucidating the Role of SET as a Key Contributor to Neurodevelopmental Disability Within the 9q34.11 Deletion Syndrome Interval.

The 9q34.11 chromosomal region contains multiple neurodevelopmental genes involved in synaptic transmission, axonal structure and neuronal maturation. Pathogenic microdeletions, duplications and single nucleotide variants in numerous genes were previously linked with neurodevelopmental disorders (NDDs). Amongst them, SET has recently been implicated in a rare NDD with speech delay and facial dysmorphism. This study reports a female with a heterozygous de novo deletion impacting SET but not other NDD-associated genes at 9q34.11. The proband was initially diagnosed with atypical Rett syndrome with overlapping clinical features of SET haploinsufficiency. The deletion was confirmed using microarray and long-read sequencing. Subsequent quantitative proteomic evaluation identified a significant decrease of SET protein in patient-derived fibroblasts compared to control lines. This study provides insights into the proband's clinical course over their 28 year diagnostic odyssey, and emphasises the benefits of early speech therapy interventions. The proband had no functional speech, but regained the capacity to meaningfully communicate and articulate a limited vocabulary in adulthood, concordant with other reported non-paediatric cases of SET-NDD. This study expands current knowledge on the genotypic and phenotypic spectra of SET-NDD, and pinpoints a smaller 9q34.11 critical region excluding upstream NDD-associated genes, STXBP1 and SPTAN1, implicating SET as a significant NDD-associated gene.

Humans↗