A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia
| Autor: | Andrea Rossi, A. de la Chapelle, Ana Belinda Campos-Xavier, C Chiesa, Antonella Forlino, Andrea Superti-Furga, Luisa Bonafé, J. Hästbacka |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Anion Transport Proteins Population CHO Cells SLC26A2 Osteochondrodysplasias Transfection medicine.disease_cause Article Multiple epiphyseal dysplasia Cricetulus Population Groups Cricetinae Genetics medicine Animals Humans Allele education Cells Cultured Finland Genetics (clinical) education.field_of_study Mutation biology Achondrogenesis Infant Newborn medicine.disease Pedigree Sulfate Transporters Dysplasia biology.protein Female Diastrophic dysplasia Anion Transport Proteins/genetics Anion Transport Proteins/metabolism Osteochondrodysplasias/genetics Osteochondrodysplasias/pathology Population Groups/genetics medicine.symptom |
| Zdroj: | Journal of Medical Genetics, vol. 45, no. 12, pp. 827-831 |
| ISSN: | 1468-6244 |
| DOI: | 10.1136/jmg.2007.057158 |
| Popis: | Background: Mutations in the sulphate transporter gene SLC26A2 (DTDST) cause a continuum of skeletal dysplasia phenotypes that includes achondrogenesis type1B (ACG1B) atelosteogenesis type 2 (AO2), diastrophic dysplasia (DTD), and recessive multiple epiphyseal dysplasia (rMED). In 1972, de la Chapelle et al reported two siblings with a lethal skeletal dysplasia, which was denoted “neonatal osseous dysplasia” and “de la Chapelle dysplasia” (DLCD). It was suggested that DLCD might be part of the SLC26A2 spectrum of phenotypes, both because of the Finnish origin of the original family and of radiographic similarities to ACG1B and AO2. Objective: To test the hypothesis whether SLC26A2 mutations are responsible for DLCD. Methods: We studied the DNA from the original DLCD family and from 7 Finnish DTD patients in whom we had identified only one copy of IVS1+2T>C, the common Finnish mutation. A novel SLC26A2 mutation was found in all subjects, inserted by site-directed mutagenesis in a vector harbouring the SLC26A2 cDNA, and expressed in sulphate transport deficient Chinese Hamster ovary (CHO) cells to measure sulphate uptake activity. Results: We identified a hitherto undescribed SLC26A2 mutation, T512K, homozygous in the affected subjects and heterozygous in both parents and in the unaffected sister. T512K was then identified as second pathogenic allele in the seven Finnish DTD subjects. Expression studies confirmed pathogenicity. Conclusions: DLCD is indeed allelic to the other SLC26A2 disorders. T512K is a second rare “Finnish” mutation that results in DLCD at homozygosity and in DTD when compounded with the milder, common Finnish mutation. |
| Databáze: | OpenAIRE |
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