title: Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population.
abstract: SLC26A2-related dysplasias encompass a spectrum of diseases: from lethal achondrogenesis type 1B (ACG1B; MIM #600972) and atelosteogenesis type 2 (AO2; MIM #256050) to classical diastrophic dysplasia (cDTD; MIM #222600) and recessive multiple epiphyseal dysplasia (rMED; MIM #226900). This study aimed at characterizing clinically, radiologically and molecularly 14 patients affected by non-lethal SLC26A2-related dysplasias and at evaluating genotype-phenotype correlation. Phenotypically, eight patients were classified as cDTD, four patients as rMED and two patients had an intermediate phenotype (mild DTD - mDTD, previously 'DTD variant'). The Arg279Trp mutation was present in all patients, either in homozygosity (resulting in rMED) or in compound heterozygosity with the known severe alleles Arg178Ter or Asn425Asp (resulting in DTD) or with the mutation c.727-1G>C (causing mDTD). The 'Finnish mutation', c.-26+2T>C, and the p.Cys653Ser, both frequent mutations in non-Portuguese populations, were not identified in any of the patients of our cohort and are probably very rare in the Portuguese population. A targeted mutation analysis for p.Arg279Trp and p.Arg178Ter in the Portuguese population allows the identification of approximately 90% of the pathogenic alleles.
authors.affiliation: Unidade de Genética Médica, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal. mafalda.barbosa@insa.min-saude.pt
authors.forename: M
authors.initials: M
authors.lastname: Barbosa
authors.forename: A B
authors.initials: AB
authors.lastname: Sousa
authors.forename: A
authors.initials: A
authors.lastname: Medeira
authors.forename: T
authors.initials: T
authors.lastname: Lourenço
authors.forename: J
authors.initials: J
authors.lastname: Saraiva
authors.forename: J
authors.initials: J
authors.lastname: Pinto-Basto
authors.forename: G
authors.initials: G
authors.lastname: Soares
authors.forename: A M
authors.initials: AM
authors.lastname: Fortuna
authors.forename: A
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: L
authors.initials: L
authors.lastname: Mittaz
authors.forename: M
authors.initials: M
authors.lastname: Reis-Lima
authors.forename: L
authors.initials: L
authors.lastname: Bonafé
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D027321:Anion Transport Proteins / Q000235:genetics*; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004392:Dwarfism / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics; D010641:Phenotype; D011174:Portugal / Q000453:epidemiology; D011859:Radiography; D000076988:Sulfate Transporters; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D027321:Anion Transport Proteins; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters