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

Atsushi Miyake, Gen Nishimura, Toru Futami, Hirofumi Ohashi, Kazuhiro Chiba, Yoshiaki Toyama, Tatsuya Furuichi, Shiro Ikegawa

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.ΔV340 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.ΔV340, 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.

Original languageEnglish
Pages (from-to)764-768
Number of pages5
JournalJournal of Human Genetics
Volume53
Issue number8
DOIs
Publication statusPublished - 2008 Aug

Fingerprint

Osteochondrodysplasias
Heterozygote
Sulfates
Phenotype
Mutation
Enchondromatosis
Diastrophic dysplasia
Desbuquois syndrome
Proteoglycans
Cartilage
Differential Diagnosis

Keywords

  • Desbuquois dysplasia
  • Diastrophic dysplasia (DTD)
  • Diastrophic dysplasia sulfate transporter (DTDST)
  • Genotype-phenotype correlation
  • Recessive form of multiple epiphyseal dysplasia (r-MED)

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

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. / Miyake, Atsushi; Nishimura, Gen; Futami, Toru; Ohashi, Hirofumi; Chiba, Kazuhiro; Toyama, Yoshiaki; Furuichi, Tatsuya; Ikegawa, Shiro.

In: Journal of Human Genetics, Vol. 53, No. 8, 08.2008, p. 764-768.

Research output: Contribution to journalArticle

Miyake, Atsushi ; Nishimura, Gen ; Futami, Toru ; Ohashi, Hirofumi ; Chiba, Kazuhiro ; Toyama, Yoshiaki ; Furuichi, Tatsuya ; Ikegawa, Shiro. / 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. In: Journal of Human Genetics. 2008 ; Vol. 53, No. 8. pp. 764-768.
@article{0140f5fdfad44977aade70459dfdb212,
title = "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",
abstract = "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.ΔV340 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.ΔV340, 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.",
keywords = "Desbuquois dysplasia, Diastrophic dysplasia (DTD), Diastrophic dysplasia sulfate transporter (DTDST), Genotype-phenotype correlation, Recessive form of multiple epiphyseal dysplasia (r-MED)",
author = "Atsushi Miyake and Gen Nishimura and Toru Futami and Hirofumi Ohashi and Kazuhiro Chiba and Yoshiaki Toyama and Tatsuya Furuichi and Shiro Ikegawa",
year = "2008",
month = "8",
doi = "10.1007/s10038-008-0305-z",
language = "English",
volume = "53",
pages = "764--768",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - 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

AU - Miyake, Atsushi

AU - Nishimura, Gen

AU - Futami, Toru

AU - Ohashi, Hirofumi

AU - Chiba, Kazuhiro

AU - Toyama, Yoshiaki

AU - Furuichi, Tatsuya

AU - Ikegawa, Shiro

PY - 2008/8

Y1 - 2008/8

N2 - 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.ΔV340 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.ΔV340, 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.

AB - 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.ΔV340 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.ΔV340, 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.

KW - Desbuquois dysplasia

KW - Diastrophic dysplasia (DTD)

KW - Diastrophic dysplasia sulfate transporter (DTDST)

KW - Genotype-phenotype correlation

KW - Recessive form of multiple epiphyseal dysplasia (r-MED)

UR - http://www.scopus.com/inward/record.url?scp=48549096525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48549096525&partnerID=8YFLogxK

U2 - 10.1007/s10038-008-0305-z

DO - 10.1007/s10038-008-0305-z

M3 - Article

C2 - 18553123

AN - SCOPUS:48549096525

VL - 53

SP - 764

EP - 768

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 8

ER -