A compound heterozygote of novel and recurrent DTDST mutations results in a novel intermediate phenotype of Desbuquois dysplasia, diastrophic dysplasia, and recessive form of multiple epiphyseal dysplasia
| Autor: | Shiro Ikegawa, Gen Nishimura, Atsushi Miyake, Tatsuya Furuichi, Hirofumi Ohashi, Yoshiaki Toyama, Toru Futami, Kazuhiro Chiba |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Anion Transport Proteins Molecular Sequence Data Genes Recessive Biology Compound heterozygosity medicine.disease_cause Osteochondrodysplasias Multiple epiphyseal dysplasia Diagnosis Differential Mice Atelosteogenesis type II Genetics medicine Animals Humans Point Mutation Amino Acid Sequence Genetics (clinical) Mutation Achondrogenesis Genetic Carrier Screening Infant Newborn Infant medicine.disease Phenotype Sulfate transport Radiography Sulfate Transporters Child Preschool Diastrophic dysplasia Female medicine.symptom |
| Zdroj: | Journal of human genetics. 53(8) |
| ISSN: | 1434-5161 |
| Popis: | Diastrophic dysplasia sulfate transporter (DTDST) is required for synthesis of sulfated proteoglycans in cartilage, and its loss-of-function mutations result in recessively inherited chondrodysplasias. The 40 or so DTDST mutations reported to date cause a group of disorders termed the diastrophic dysplasia (DTD) group. The group ranges from the mildest recessive form of multiple epiphyseal dysplasia (r-MED) through the most common DTD to perinatally lethal atelosteogenesis type II and achondrogenesis 1B. Furthermore, the relationship between DTDST mutations, their sulfate transport function, and disease phenotypes has been described. Here we report a girl with DTDST mutations: a compound heterozygote of a novel p.T266I mutation and a recurrent p.DeltaV340 mutation commonly found in severe phenotypes of the DTD group. In infancy, the girl presented with skeletal manifestations reminiscent of Desbuquois dysplasia, another recessively inherited chondrodysplasia, the mutations of which have never been identified. Her phenotype evolved with age into an intermediate phenotype between r-MED and DTD. Considering her clinical phenotypes and known phenotypes of p.DeltaV340, p.T266I was predicted to be responsible for mild phenotypes of the DTD group. Our results further extend the phenotypic spectrum of DTDST mutations, adding Desbuquois dysplasia to the list of differential diagnosis of the DTD group. |
| Databáze: | OpenAIRE |
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