Childhood-related neural genotype–phenotype in ATP1A3 mutations: comprehensive analysis

Muthaffar, Osama Y.; Alqarni, Asma; Shafei, Jumana A.; Bahowarth, Sarah Y.; Alyazidi, Anas S.; Naseer, Muhammad Imran

doi:10.1007/s13258-023-01481-8

Cited by 1 publication

(1 citation statement)

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“…The mutation can impair perforin-mediated cytotoxicity, leading to defective immune surveillance and hyperinflammatory responses [ 39 ]. Additionally, an ATP1A3 variant have been associated with a spectrum of neurological disorders which includes alternating hemiplegia of childhood (AHC) and rapid-onset dystonia-parkinsonism (RDP) [ 40 ]. Interpreting ATP1A3 mutations involves assessing their impact on ion transport and neuronal excitability [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical description and evaluation of 30 pediatric patients with ultra-rare diseases: A multicenter study with real-world data from Saudi Arabia

Muthaffar,

Alazhary,

Alyazidi

et al. 2024

PLoS ONE

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Background With the advancement of next-generation sequencing, clinicians are now able to detect ultra-rare mutations that are barely encountered by the majority of physicians. Ultra-rare and rare diseases cumulatively acquire a prevalence equivalent to type 2 diabetes with 80% being genetic in origin and more prevalent among high consanguinity communities including Saudi Arabia. The challenge of these diseases is the ability to predict their prevalence and define clear phenotypic features. Methods This is a non-interventional retrospective multicenter study. We included pediatric patients with a pathogenic variant designated as ultra-rare according to the National Institute for Clinical Excellence’s criteria. Demographic, clinical, laboratory, and radiological data of all patients were collected and analyzed using multinomial regression models. Results We included 30 patients. Their mean age of diagnosis was 16.77 months (range 3–96 months) and their current age was 8.83 years (range = 2–15 years). Eleven patients were females and 19 were males. The majority were of Arab ethnicity (96.77%). Twelve patients were West-Saudis and 8 patients were South-Saudis. SCN1A mutation was reported among 19 patients. Other mutations included SZT2, ROGDI, PRF1, ATP1A3, and SHANK3. The heterozygous mutation was reported among 67.86%. Twenty-nine patients experienced seizures with GTC being the most frequently reported semiology. The mean response to ASMs was 45.50% (range 0–100%). Conclusion The results suggest that ultra-rare diseases must be viewed as a distinct category from rare diseases with potential demographic and clinical hallmarks. Additional objective and descriptive criteria to detect such cases are needed.

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Section: Discussionmentioning

confidence: 99%