Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians
| Autor: | T. Thomas, A. M. Gagnon, M. Lambert, Bernard Brais, Guy A. Rouleau, Albert Larbrisseau, Michel Vanasse, G. Marleau, I. Gosselin, A. M. Sarrazin, A. St-Denis, Marie-Josée Dicaire, D. Gaudet, K. Roddier |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Genotype DNA Mutational Analysis Nonsense mutation Nerve Tissue Proteins Locus (genetics) Protein Serine-Threonine Kinases Cohort Studies Minor Histocompatibility Antigens WNK Lysine-Deficient Protein Kinase 1 Hereditary sensory and autonomic neuropathy Prevalence HSN2 Humans Medicine Genetic Predisposition to Disease Genetic Testing Peripheral Nerves Hereditary Sensory and Autonomic Neuropathies Child Gene Aged Genetic testing Genetics Chromosomes Human Pair 12 Base Sequence medicine.diagnostic_test business.industry Intracellular Signaling Peptides and Proteins Quebec Chromosome Mapping Infant Middle Aged medicine.disease Phenotype Pedigree Child Preschool Mutation Female Neurology (clinical) business |
| Zdroj: | Neurology. 64:1762-1767 |
| ISSN: | 1526-632X 0028-3878 |
| Popis: | Background: Hereditary sensory and autonomic neuropathy type 2 (HSAN2; MIM 201300) is a rare recessive neuropathy typically diagnosed in the first decade. The 1973 study of a French Canadian family led to the definition of HSAN2. Objectives: To demonstrate that the apparent higher prevalence of HSAN2 in Quebec is due to the presence of two HSN2 mutations and that carriers of different mutations appear to have a similar phenotype. Methods: Through attending physicians, the authors recruited French Canadian patients with HSAN2. Exclusion of linkage to the known HSAN loci and linkage to the HSAN2 was performed using standard methods. Sequencing of the HSN2 gene was used to uncover the causal mutations. Results: A large cluster of HSAN2 patients comprising 16 affected individuals belonging to 13 families was identified. The mode of inheritance is clearly autosomal recessive. All patients originated from southern Quebec, and 75% are from the Lanaudiere region. Whereas linkage to the HSAN1, 3, and 4 loci was excluded, linkage to the 12p13.33 HSAN2 locus was confirmed. Sequencing of the HSN2 gene uncovered two French Canadian mutations and a novel nonsense mutation in a patient of Lebanese origin, all predicted to lead to truncations of the HSN2 protein. The comparison of clinical variables between patients with different genotypes does not suggest any difference in phenotype. Conclusions: Two founder mutations are responsible for the apparently higher prevalence of HSAN2 in French Canadians. Genotype-phenotype correlation does not suggest any significant clinical variability. |
| Databáze: | OpenAIRE |
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