HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome.

Abstract
Weill-Marchesani syndrome (WMS) is characterized by the association of short stature; brachydactyly; joint stiffness; eye anomalies, including microspherophakia and ectopia of the lenses; and, occasionally, heart defects. We have recently mapped a gene for the autosomal recessive form of WMS to chromosome 19p13.3-p13.2, in a 12.4-cM interval. Here, we report null mutations in a member of the extracellular matrix protease family, the gene encoding ADAMTS10, a disintegrin and metalloprotease with thrombospondin motifs. A total of three distinct mutations were identified in two consanguineous families and in one sporadic WMS case, including one nonsense mutation (R237X) and two splice mutations (1190+1G-->A and 810+1G-->A). ADAMTS10 expression studies using reverse-transcriptase polymerase chain reaction, northern blot, and dot-blot analyses showed that ADAMTS10 is expressed in skin, fetal chondrocytes, and fetal and adult heart. Moreover, electron microscopy and immunological studies of the skin fibroblasts from the patients confirmed impairment of the extracellular matrix. We conclude, therefore, that ADAMTS10 plays a major role in growth and in skin, lens, and heart development in humans.
AuthorsNathalie Dagoneau, Catherine Benoist-Lasselin, Céline Huber, Laurence Faivre, André Mégarbané, Abdulrahman Alswaid, Hélène Dollfus, Yves Alembik, Arnold Munnich, Laurence Legeai-Mallet, Valérie Cormier-Daire
JournalAmerican journal of human genetics (Am J Hum Genet) Vol. 75 Issue 5 Pg. 801-6 (Nov 2004) ISSN: 0002-9297 [Print] United States
PMID15368195 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • DNA Primers
  • Extracellular Matrix Proteins
  • ADAM Proteins
  • ADAMTS Proteins
  • ADAMTS10 protein, human
  • Metalloendopeptidases
Topics
  • ADAM Proteins
  • ADAMTS Proteins
  • Abnormalities, Multiple (genetics)
  • Actins (metabolism)
  • Base Sequence
  • Blotting, Northern
  • Child
  • DNA Primers
  • Dwarfism (genetics)
  • Extracellular Matrix Proteins (genetics)
  • Eye Abnormalities (genetics)
  • Fibroblasts (immunology, ultrastructure)
  • Gene Components
  • Gene Expression
  • Genes, Recessive (genetics)
  • Humans
  • Immunoblotting
  • Metalloendopeptidases (genetics)
  • Microscopy, Electron
  • Molecular Sequence Data
  • Mutation (genetics)
  • Pedigree
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Syndrome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: