Recessive multiple epiphyseal dysplasia (rMED): phenotype delineation in eighteen homozygotes for DTDST mutation R279W
| Autor: | Sheila Unger, Diana Ballhausen, William G. Cole, Jacqueline T. Hecht, Andrea Superti-Furga, Paulien A Terhal, J. Spranger, Daniel H. Cohn, G. Bellus, Luisa Bonafé, M. Classen, Bernhard Zabel, Ben C.J. Hamel |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Adolescent Anion Transport Proteins Genes Recessive Biology SLC26A2 Arginine Osteochondrodysplasias Short stature Multiple epiphyseal dysplasia Genetics medicine Humans Child Genetics (clinical) Achondrogenesis Sulfates Point mutation Homozygote Tryptophan Chromosome Mapping Membrane Transport Proteins Biological Transport Middle Aged medicine.disease Phenotype Genetic defects of metabolism [UMCN 5.1] Amino Acid Substitution Dysplasia Sulfate Transporters Mutation (genetic algorithm) Mutation Mutation testing biology.protein Female medicine.symptom Carrier Proteins Letter to JMG |
| Zdroj: | Journal of Medical Genetics, 40, 1, pp. 65-71 Journal of Medical Genetics, 40, 65-71 |
| ISSN: | 1468-6244 0022-2593 |
| Popis: | Multiple epiphyseal dysplasia (MED) is a generalised skeletal dysplasia that although relatively mild is associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. In the past, the disorder was subdivided into the milder Ribbing type, usually with flattened epiphyses,1 and the more severe Fairbank type with round epiphyses,2 but many cases were not classifiable as clearly either type.3 MED can be caused by mutations in at least six separate genes: COMP ,4–7 collagen IX ( COL9A1 , COL9A2 , and COL9A3 ),8–13 matrilin 3 ( MATN3 ),15 and the sulphate transporter, DTDST ( DTDST/SLC26A2 ). We have previously reported an adult with a recessively inherited form of MED (rMED) characterised by club feet, double layered patellae, and normal stature, who was homozygous for the mutation 862c>t/R279W in the DTDST gene, previously associated with the achondrogenesis 1B-atelosteogenesis 2-diastrophic dysplasia spectrum. We now report on a group of 18 subjects who are homozygous for this point mutation, allowing a comprehensive assessment of this particular MED phenotype. Distinction of rMED is important because of its recessive inheritance (unlike other MED types) and genetic counselling implications. The frequency of the R279W mutation and the number of subjects with molecularly proven rMED identified since its description suggest that rMED may be more common than hitherto assumed. Blood or genomic DNA was sent to the Zurich centre for DTDST mutation analysis because of clinical and radiographic signs similar to the reported case of rMED,20 or because of a clinical diagnosis of MED and negative mutation analysis of COMP or collagen IX genes. Genomic DNA was extracted from blood leucocytes using standard protocols and was subjected to DTDST mutation analysis. The fragment of interest, that is, the 5′ part of exon … |
| Databáze: | OpenAIRE |
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