期刊
NEUROLOGY
卷 80, 期 23, 页码 2106-2111出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e318295d789
关键词
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资金
- National Institute of Neurological Disorders and Stroke/Office of Rare Diseases (ORD) [1U54NS065712-01]
- Department of Health's National Institute for Health Research Biomedical Research Centres
- Medical Research Council
- Muscular Dystrophy Campaign
- MRC [G108/638, G1001253, MR/J004758/1, G0802760, MR/K000608/1] Funding Source: UKRI
- Medical Research Council [G1001253, G0802760, MR/K000608/1, G108/638, MR/J004758/1] Funding Source: researchfish
Objective: To describe the clinical and neurophysiologic phenotype of a family with hereditary sensory and autonomic neuropathy type 1 (HSANI) due to a novel mutation in SPTLC2 and to characterize the biochemical properties of this mutation. Methods: We screened 107 patients with HSAN who were negative for other genetic causes for mutations in SPTLC2. The biochemical properties of a new mutation were characterized in cell-free and cell-based activity assays. Results: A novel mutation (A182P) was found in 2 subjects of a single family. The phenotype of the 2 subjects was an ulcero-mutilating sensory-predominant neuropathy as described previously for patients with HSANI, but with prominent motor involvement and earlier disease onset in the first decade of life. Affected patients had elevated levels of plasma 1-deoxysphingolipids (1-deoxySLs). Biochemically, the A182P mutation was associated with a reduced canonical activity but an increased alternative activity with alanine, which results in largely increased 1-deoxySL levels, supporting their pathogenicity. Conclusion: This study confirms that mutations in SPTLC2 are associated with increased deoxySL formation causing HSANI.
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