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Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic.

ABSTRACT: Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia are recessive spondyloepimetaphyseal dysplasias caused by loss-of-function mutations in dymeclin (Dym), a gene with previously unknown function. Here we report that Dym-deficient mice display defects in endochondral bone formation similar to that of Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia, demonstrating functional conservation between the two species. Dym-mutant cells display multiple defects in vesicle traffic, as evidenced by enhanced dispersal of Golgi markers in interphase cells, delayed Golgi reassembly after brefeldin A treatment, delayed retrograde traffic of an endoplasmic reticulum-targeted Shiga toxin B subunit, and altered furin trafficking; and the Dym protein associates with multiple cellular proteins involved in vesicular traffic. These results establish dymeclin as a novel protein involved in Golgi organization and intracellular vesicle traffic and clarify the molecular basis for chondrodysplasia in mice and men.

SUBMITTER: Osipovich AB

PROVIDER: S-EPMC2571016 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic.

Osipovich Anna B AB Jennings Jennifer L JL Lin Qing Q Link Andrew J AJ Ruley H Earl HE

Proceedings of the National Academy of Sciences of the United States of America 20081013 42

Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia are recessive spondyloepimetaphyseal dysplasias caused by loss-of-function mutations in dymeclin (Dym), a gene with previously unknown function. Here we report that Dym-deficient mice display defects in endochondral bone formation similar to that of Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia, demonstrating functional conservation between the two species. Dym-mutant cells display multiple defects in vesicle traffic, as e ...[more]

PMID: 18852472

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Project description:IntroductionDyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive type of skeletal dysplasia. It is characterized by the association of progressive spondyloepimetaphyseal dysplasia (SEMD), microcephaly, mental retardation (MR), and coarse facies. The radiographic appearance of generalized platyspondyly with double-humped end plates and the lace-like appearance of iliac crests are pathognomonic and distinctive of DMC syndrome. The disorder results from mutations in the DYM gene mapped in the 18q12-12.1 chromosomal region.Materials and methodsIn this report, we studied 15 Egyptian cases with DMC syndrome from nine unrelated families. We aimed to emphasize the characteristic clinical and radiological features in order to differentiate the condition from other SEMDs and mucopolysaccharidosis (MPS). Patients were subjected to detailed history taking, three-generation family pedigree analysis, complete physical examination, anthropometric measurements, quantitative estimation, and two-dimensional electrophoresis of glycosaminoglycans in the urine and measurement of α-l-iduronidase and galactose-6-sulfatase enzyme activities to exclude Hurler and Morquio diseases (MPS type I and MPS type IVA), respectively. Other investigations were carried out whenever indicated. All patients were the offspring of consanguineous apparently normal parents. Positive family history and similarly affected sibs were noted, confirming the autosomal recessive inheritance pattern of the syndrome. Short stature, microcephaly, variable degree of MR, and coarse facies were constant features. The frequency of characteristic orthopedic and radiological findings was reported. Orthopedic surgical intervention was carried out for two patients.ConclusionsThe study concluded that DMC syndrome may be more frequent in Egypt than previously thought, especially due to misdiagnosis. Characteristic facial dysmorphism, body habitus, and pathognomonic radiological signs suggest the diagnosis and differentiate it from other types of SEMDs and MPS for proper genetic counseling and management.

Dataset Information

Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic.

Publications

Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic.

Similar Datasets

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