Acid-sensing ion channels (ASICs) are members of the voltage-insensitive, amiloride-sensitive degenerin/epithelial Na channel family of cation channels and have been shown to mediate pain associated with tissue acidosis after inflammation or injury; however, the expression and role of ASICs in gastrointestinal tract of Henoch-Schönlein purpura (HSP) patients were still uncertain.
The results showed that there was a significant increase in the mean relative optical density of ASIC2 and ASIC3 but not ASIC1a in the lining epithelium and glandular tubes of gastric mucosa from HSP patients with HSP.
Using whole-exome sequencing, we identified a dominantly inherited heterozygous variant c.1064G > A (p.G355D) in ATAD3A in a mother presenting with hereditary spastic paraplegia (HSP) and axonal neuropathy and her son with dyskinetic cerebral palsy, both with disease onset in childhood.
This may suggest a different disease mechanism with more prominent axonal degeneration in these two types of HSP when compared with HSP due to spastin and atlastin mutations.
These data suggest that spastin and atlastin function in the same biochemical pathway and that it is the cytoplasmic function of spastin which is important for the pathogenesis of HSP.
Mutations spread across atlastin isoform 1 (atlastin-1) have been identified in patients suffering from hereditary spastic paraplegia (HSP), a neurodegenerative disorder affecting motor neuron function in the lower extremities.
Overall, the comparison of the clinical data for all SPG3A-HSP families reported to date failed to reveal any genotype/phenotype correlation as demonstrated for other forms of AD-HSP.
Our results add to a growing number of HSP disease-associated variants and confirm the high prevalence of atlastin, spastin, and REEP1 mutations in the HSP patient population.
Evidence was obtained for linkage to a locus on chromosome 14q that is distinct from the SPG3 locus for autosomal dominant HSP (D14S77: lod score of 4.20 at zero recombination).
<b>Results:</b> Fifty four patients with genetically confirmed HSP diagnosis, 36 with spastic paraplegia type 4 (SPG4), 5 SPG11, 4 SPG5, 4 cerebrotendinous xanthomatosis (CTX), 3 SPG7 and 2 SPG3A, and 10 healthy, unrelated control subjects, with similar age, sex, and education participated in the study.
The family with the ATL1 c.1204T>G mutation exhibited male-lethality, female infancy-onset, and pseudo- X-linked dominant transmission, which had never been previously reported for HSP.
Our combined findings show that homozygosity for the ATL1 missense variant remains the only plausible cause of HSP, whereas heterozygous carriers are asymptomatic.
Mutations in the SPG4 gene (spastin) and in the SPG3A gene (atlastin) account for the majority of 'pure' autosomal dominant form of hereditary spastic paraplegia (HSP).
Mutations in 3 genes encoding proteins that work together to shape the ER into sheets and tubules - receptor accessory protein 1 (REEP1), atlastin-1 (ATL1), and spastin (SPAST) - have been found to underlie many cases of HSP in Northern Europe and North America.