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.
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.
Miyake
Atsushi
A
Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.|Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
Nishimura
Gen
G
Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Kiyose, Tokyo, Japan.
Futami
Toru
T
Department of Orthopaedic Surgery, Shiga Medical Center for Children, Moriyama, Shiga, Japan.
Ohashi
Hirofumi
H
Department of Heredity Clinic, Saitama Children's Medical Center, Saitama, Japan.
Chiba
Kazuhiro
K
Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
Toyama
Yoshiaki
Y
Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
Furuichi
Tatsuya
T
Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Ikegawa
Shiro
S
Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. sikegawa@ims.u-tokyo.ac.jp.
D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics*; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D011859:Radiography; D000076988:Sulfate Transporters
D027321:Anion Transport Proteins; C089651:SLC26A2 protein, human; D000076988:Sulfate Transporters