Distal truncation of KCC3 in non-French Canadian HMSN/ACC families
| العنوان: | Distal truncation of KCC3 in non-French Canadian HMSN/ACC families |
|---|---|
| المؤلفون: | Michèl A.A.P. Willemsen, Mustafa Tekin, Nicolas Dupré, Masoud Shekarabi, Jean-Baptiste Rivière, Guy A. Rouleau, Frédéric Charron, Jürgen Horst, Gülhis Deda, M. M. Lippert, Adèle Salin-Cantegrel, Claudia Gaspar, Liliane Karemera, A. Krause, Jean-Yves Lapointe, R. Jarrar |
| المصدر: | Neurology, 69, 13, pp. 1350-5 Neurology, 69, 1350-5 |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Male, Genotype, Population, DNA Mutational Analysis, Inheritance Patterns, Biology, medicine.disease_cause, Nervous System Malformations, White People, Exon, Xenopus laevis, Mutant protein, medicine, Animals, Humans, Genetic Predisposition to Disease, Genetic Testing, Hereditary Sensory and Autonomic Neuropathies, education, Agenesis of the corpus callosum, Genetics, Mutation, education.field_of_study, Symporters, Haplotype, Cell Membrane, Wild type, Quebec, Exons, medicine.disease, Neuromuscular development and genetic disorders [UMCN 3.1], Pedigree, Haplotypes, Oocytes, Female, Neurology (clinical), Agenesis of Corpus Callosum, Hereditary motor and sensory neuropathy |
| الوصف: | Background: Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a severe and progressive autosomal recessive polyneuropathy. Mutations in the potassium-chloride cotransporter 3 gene (KCC3) were identified as responsible for HMSN/ACC in the French Canadian (FC) population. In the present study, the authors were interested in finding new mutations in non-FC populations, assessing the activity of mutant proteins and refining genotype-phenotype correlations. Methods: The authors screened KCC3 for mutations using direct sequencing in six non-FC HMSN/ACC families. They then assessed the functionality of the most common mutant protein using a flux assay in Xenopus laevis oocytes. Results: The authors identified mutations in exon 22 of KCC3: a novel mutation (del + 2994-3003; E1015X) in one family, as well as a known mutation (3031C→T; R1011X) found in five unrelated families and associated with two different haplotypes. The function of the cotransporter was abolished, although a limited amount of mutant proteins were correctly localized at the membrane. Conclusions: KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin, and are the most common cause of HMSN/ACC in the non–French Canadian (FC) families analyzed so far. Therefore, for genetic analysis, exon 22 screening should be prioritized in non-FC populations. Finally, the R1011X mutation leads to the abrogation of KCC3’s function in Xenopus laevis oocytes, likely due to impaired transit of the cotransporter. GLOSSARY: ANOVA = analysis of variance; CTD = C-terminal domain; FC = French Canadian population; HMSN/ACC = hereditary motor and sensory neuropathy with agenesis of the corpus callosum; KCC3 = potassium-chloride cotransporter 3; mut = mutated sequence; NGS = normal goat serum; RVD = regulatory volume decrease; WT = wild type sequence. |
| تدمد: | 1526-632X 0028-3878 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3cf2272099b52134969c4195b1b5d90Test https://pubmed.ncbi.nlm.nih.gov/17893295Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....e3cf2272099b52134969c4195b1b5d90 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1526632X 00283878 |
|---|