title: Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign.
abstract: Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene result in a family of skeletal dysplasias, which comprise lethal (achondrogenesis type 1B and atelosteogenesis type 2) and non-lethal conditions (diastrophic dysplasia and recessive multiple epiphyseal dysplasia (rMED)). The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and "double layered" patella. We describe three patients with rMED caused by a previously unreported homozygous mutation in the DTDST gene. The three patients (from two families) were born to healthy, non-consanguineous parents. All developed signs of hip dysplasia in early childhood and two had episodes of recurrent patella dislocation. Two underwent bilateral total hip replacements at ages 13 and 14 years. The feet, external ears, and palate were normal. Stature was normal in all cases. Radiographs showed dysplastic femoral heads, mild generalized epiphyseal dysplasia, abnormal patella ossification, and normal hands and feet. Direct sequence analysis of genomic DNA demonstrated a homozygous 1984T > A (C653S) change in the DTDST gene in all patients. The clinically normal parents were heterozygous for the change. This is the first description of a homozygous C653S mutation of the DTDST gene. Hip dysplasia and patella hypermobility dominates the otherwise mild phenotype. These patients further expand the range of causative mutations in the DTD skeletal dysplasia family.
authors.affiliation: Center for the Study of Heritable Connective Tissue Diseases, Research Institute, University of Toronto, Toronto, Ontario M5G 1X8, Canada. outi.makitie@helsinki.fi
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
authors.forename: Ravi
authors.initials: R
authors.lastname: Savarirayan
authors.forename: Luisa
authors.initials: L
authors.lastname: Bonafé
authors.forename: Stephen
authors.initials: S
authors.lastname: Robertson
authors.forename: Miki
authors.initials: M
authors.lastname: Susic
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: William G
authors.initials: WG
authors.lastname: Cole
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010329:Patella / Q000002:abnormalities*; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters; D004247:DNA