title: A compound heterozygote SLC26A2 mutation resulting in robin sequence, mild limbs shortness, accelerated carpal ossification, and multiple epiphysial dysplasia in two Brazilian sisters. A new intermediate phenotype between diastrophic dysplasia and recessive multiple epiphyseal dysplasia.
abstract: Mutations in solute carrier family 26 (sulfate transporter), member 2 (SLC26A2) gene result in a spectrum of autosomal recessive chondrodysplasias that range from the mildest recessive form of multiple epiphysial dysplasia (rMED) through the most common diastrophic dysplasia (DTD) to lethal atelosteogenesis type II and achondrogenesis IB. The clinical variability has been ascribed to quantitative effect of mutations of the sulfate transporter activity. Here we describe two Brazilian sisters, born to healthy and non consanguineous parents, with Robin sequence, mild shortening of upper and lower limbs, brachymetacarpalia/tarsalia, additional and accelerated carpal ossification, marked genu valgum, and multiple epiphysial dysplasia. This phenotype was intermediate between DTD and rMED, and both girls have a compound heterozygous mutations for the SLC26A2, a Finnish founder mutation (c.-26 + 2T>C), and R279W. This combination of mutations has been observed in individuals with different phenotypes, including DTD, DTD variant, and rMED. The distinct phenotype of our cases reinforces the hypothesis that other factors may be influencing the phenotype as previously suggested.
authors.affiliation: Department of Clinical Genetics, Hospital of Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRAC/USP), Bauru, São Paulo, Brazil. roselizc@centrinho.usp.br
authors.forename: Roseli Maria
authors.initials: RM
authors.lastname: Zechi-Ceide
authors.forename: Priscila Padilha
authors.initials: PP
authors.lastname: Moura
authors.forename: Salmo
authors.initials: S
authors.lastname: Raskin
authors.forename: Antonio
authors.initials: A
authors.lastname: Richieri-Costa
authors.forename: Maria Leine
authors.initials: ML
authors.lastname: Guion-Almeida
mesh_terms: D000328:Adult; D027321:Anion Transport Proteins / Q000235:genetics*; D001938:Brazil; D002348:Carpal Bones / Q000473:pathology*; D002648:Child; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics*; D005121:Extremities / Q000473:pathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias; D010012:Osteogenesis; D010641:Phenotype; D010855:Pierre Robin Syndrome / Q000175:diagnosis / Q000235:genetics*; D035781:Siblings; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters
keywords: Robin sequence; SLC26A2 gene; diastrophic dysplasia; recessive multiple epiphyseal dysplasia