Clinical and molecular spectrum of a large Egyptian cohort with ALS2-related disorders of infantile-onset of clinical continuum IAHSP/JPLS.

Autor: Zaki MS; Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Sharaf-Eldin WE; Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Rafat K; Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Elbendary HM; Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Kamel M; Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt., Elkhateeb N; Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.; Department of Clinical Genetics, Cambridge University Hospitals, Cambridge, UK., Noureldeen MM; Department of Pediatrics, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt., Abdeltawab MA; Department of Pediatrics, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt., Sadek AA; Pediatric Neurology Department, Faculty of Medicine, Sohag University, Sohag, Egypt., Essawi ML; Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Lau T; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London, UK., Murphy D; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London, UK., Abdel-Hamid MS; Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Holuden H; Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London, UK., Issa MY; Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Gleeson JG; Department of Neurosciences, University of California, San Diego, La Jolla, USA.; Rady Children's Hospital, Rady Children's Institute for Genomic Medicine, San Diego, La Jolla, USA.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2023 Aug; Vol. 104 (2), pp. 238-244. Date of Electronic Publication: 2023 Apr 13.
DOI: 10.1111/cge.14338
Abstrakt: This study presents 46 patients from 23 unrelated Egyptian families with ALS2-related disorders without evidence of lower motor neuron involvement. Age at onset ranged from 10 months to 2.5 years, featuring progressive upper motor neuron signs. Detailed clinical phenotypes demonstrated inter- and intrafamilial variability. We identified 16 homozygous disease-causing ALS2 variants; sorted as splice-site, missense, frameshift, nonsense and in-frame in eight, seven, four, three, and one families, respectively. Seven of these variants were novel, expanding the mutational spectrum of the ALS2 gene. As expected, clinical severity was positively correlated with disease onset (p = 0.004). This work provides clinical and molecular profiles of a large single ethnic cohort of patients with ALS2 mutations, and suggests that infantile ascending hereditary spastic paralysis (IAHSP) and juvenile primary lateral sclerosis (JPLS) are belonged to one entity with no phenotype-genotype correlation.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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