NovelOCTN2 mutations: No genotype-phenotype correlations: Early carnitine therapy prevents cardiomyopathy
| Autor: | G. T. N. Besley, Rodney J. Pollitt, Linda De Meirleir, Ivo Barić, Ingrid Tein, Carlo Dionisi-Vici, Ljerka Cvitanovic-Sojat, Anne Marie Lamhonwah, P. Divry, Simon E. Olpin, Miljenka Maradin, Russell Onizuka, Christine Vianey-Saban, Nathalie Guffon, Ksenija Fumić |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Organic Cation Transport Proteins SLC22A5 medicine.disease_cause Frameshift mutation Structure-Activity Relationship Exon Carnitine Internal medicine Gene duplication Genotype medicine Humans Child Solute Carrier Family 22 Member 5 Genetics (clinical) Mutation biology Membrane Proteins Heart Pedigree Endocrinology Child Preschool biology.protein Female Cardiomyopathies Carrier Proteins Primary Carnitine Deficiency medicine.drug |
| Zdroj: | American Journal of Medical Genetics. 111:271-284 |
| ISSN: | 1096-8628 0148-7299 |
| Popis: | Primary systemic carnitine deficiency or carnitine uptake defect (OMIM 212140) is a potentially lethal, autosomal recessive disorder characterized by progressive infantile-onset cardiomyopathy, weakness, and recurrent hypoglycemic hypoketotic encephalopathy, which is highly responsive to L-carnitine therapy. Molecular analysis of the SLC22A5 (OCTN2) gene, encoding the high-affinity carnitine transporter, was done in 11 affected individuals by direct nucleotide sequencing of polymerase chain reaction products from all 10 exons. Carnitine uptake (at Km of 5 microM) in cultured skin fibroblasts ranged from 1% to 20% of normal controls. Eleven mutations (delF23, N32S, and one 11-bp duplication in exon 1; R169W in exon 3; a donor splice mutation [IVS3+1 G > A] in intron 3; frameshift mutations in exons 5 and 6; Y401X in exon 7; T440M, T468R and S470F in exon 8) are described. There was no correlation between residual uptake and severity of clinical presentation, suggesting that the wide phenotypic variability is likely related to exogenous stressors exacerbating carnitine deficiency. Most importantly, strict compliance with carnitine from birth appears to prevent the phenotype. |
| Databáze: | OpenAIRE |
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