Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.

Détails

ID Serval
serval:BIB_DE2864648475
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia.
Périodique
Human Genetics
Auteur(s)
Rossi A., van der Harten H.J., Beemer F.A., Kleijer W.J., Gitzelmann R., Steinmann B., Superti-Furga A.
ISSN
0340-6717 (Print)
ISSN-L
0340-6717
Statut éditorial
Publié
Date de publication
1996
Volume
98
Numéro
6
Pages
657-661
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Mutations in the diastrophic dysplasia sulfate transporter gene DTDST have been associated with a family of chondrodysplasias that comprises, in order of increasing severity, diastrophic dysplasia (DTD), atelosteogenesis type 2 (AO2), and achondrogenesis type 1B (ACG1B). To learn more about the molecular basis of DTDST chondrodysplasias and about genotype-phenotype correlations, we studied fibroblast cultures of three new patients: one with AO-2, one with DTD, and one with an intermediate phenotype (AO2/DTD). Reduced incorporation of inorganic sulfate into macromolecules was found in all three. Each of the three patients was found to be heterozygous for a c862t transition predicting a R279W substitution in the third extracellular loop of DTDST. In two patients (DTD and AO2/DTD), no other structural mutation was found, but polymerase chain reaction amplification and single-strand conformation polymorphism analysis of fibroblast cDNA showed reduced mRNA levels of the wild-type DTDST allele: these two patients may be compound heterozygotes for the "Finnish" mutation (as yet uncharacterized at the DNA level), which causes reduced expression of DTDST. The third patient (with AO2) had the R279W mutation compounded with a novel mutation, the deletion of cytosine 418 (delta c418), predicting a frameshift with premature termination. Also the delta c418 allele was underrepresented in the cDNA, in accordance with previous observations that premature stop codons reduce mRNA levels. The presence of the DTDST R279W mutation in a total of 11 patients with AO2 or DTD emphasizes the overlap between these conditions. This mutation has not been found so far in 8 analyzed ACG1B patients, suggesting that it allows some residual activity of the sulfate transporter.
Mots-clé
Anion Transport Proteins, Biological Transport/genetics, Carrier Proteins/genetics, Cells, Cultured, DNA Mutational Analysis, Exostoses, Multiple Hereditary/genetics, Exostoses, Multiple Hereditary/pathology, Fibroblasts/metabolism, Genotype, Humans, Infant, Newborn, Male, Membrane Transport Proteins, Phenotype, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Sulfates/metabolism
Pubmed
Web of science
Création de la notice
14/03/2011 17:14
Dernière modification de la notice
20/08/2019 17:02
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