General Agreement Between the United States and Norway Relating to Exports
In: American journal of international law: AJIL, Band 12, Heft S3, S. 246-259
ISSN: 2161-7953
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In: American journal of international law: AJIL, Band 12, Heft S3, S. 246-259
ISSN: 2161-7953
In: Communist viewpoint: a theoretical and political journal, Band 19, Heft 1, S. 22-28
ISSN: 0010-3756
In: Journal of management education: the official publication of the Organizational Behavior Teaching Society, Band 11, Heft 3, S. 86-94
ISSN: 1552-6658
In: Journal of business communication: JBC, Band 26, Heft 2, S. 123-141
ISSN: 1552-4582
In: Journal of management education: the official publication of the Organizational Behavior Teaching Society
ISSN: 1552-6658
In: Plant Nutrition, S. 32-33
In: Plant Nutrition, S. 616-617
Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.
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