Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2.
Neurology
; 80(23): 2106-11, 2013 Jun 04.
Article
em En
| MEDLINE
| ID: mdl-23658386
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esfingolipídeos
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Neuropatias Hereditárias Sensoriais e Autônomas
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Serina C-Palmitoiltransferase
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Mutação
Limite:
Adult
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article