Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population

• Published in: Clinical genetics 2011-12, Vol.80 (6), p.550-557
• Main Authors: Barbosa, M, Sousa, AB, Medeira, A, Lourenço, T, Saraiva, J, Pinto-Basto, J, Soares, G, Fortuna, AM, Superti-Furga, A, Mittaz, L, Reis-Lima, M, Bonafé, L
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; Anion Transport Proteins - genetics; Biological and medical sciences; Body Height; Child; Child, Preschool; Cohort Studies; diastrophic dysplasia; Diseases of the osteoarticular system; Dwarfism - diagnosis; Dwarfism - diagnostic imaging; Dwarfism - epidemiology; Dwarfism - genetics; European Continental Ancestry Group - genetics; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic Association Studies; Genetic disorders; Genetic Testing; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Genotype & phenotype; Humans; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; Molecular and cellular biology; Mutation; Osteochondrodysplasias - diagnosis; Osteochondrodysplasias - diagnostic imaging; Osteochondrodysplasias - genetics; Phenotype; phenotype correlation; Portugal - epidemiology; Radiography; recessive multiple epiphyseal dysplasia; Skeletal system; SLC26A2; sulfate transporter; Young Adult
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2010.01595.x

Barbosa M, Sousa AB, Medeira A, Lourenço T, Saraiva J, Pinto‐Basto J, Soares G, Fortuna AM, Superti‐Furga A, Mittaz L, Reis‐Lima M, Bonafé L. Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population. 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.