Another Mutation Found for Rare Skeletal Disorder

Researchers studying the rare inherited skeletal disorder mandibuloacral dysplasia (MAD) have found a mutation in the ZMPSTE24 gene in a patient suffering from the syndrome but lacking the mutation in the LMNA gene that usually characterizes the disorder.

MAD is a rare, genetically and phenotypically heterogeneous, autosomal recessive disorder characterized by skeletal abnormalities. Previous studies had shown that a mutation in the LMNA gene, which encodes the proteins lamin A and lamin C, components of the membrane of the cell nucleus, was linked to the development of the syndrome. In the current study, which was published in the August 15, 2003, issue of Human Molecular Genetics, investigators at the University of Texas Southwestern Medical Center (Dallas, USA) focused their attention on a mutation in the ZMPSTEA24 gene that they found in a MAD patient who lacked the LMNA mutation.

They found that ZMPSTEA24 produced a zinc metalloproteinase enzyme that played a critical role in the synthesis of active lamin A. Senior author Dr. Abhimanyu Garg, professor of internal medicine at the University of Texas Southwestern Medical Center explained, "It was known that a mutation in LMNA caused MAD, but in several of the individuals that we studied LMNA was normal. This led us to look at other genes that were associated with lamin A production. We considered ZMPSTE24 as a candidate gene based on recent reports that deletion of this gene in mice resulted in the development of similar physical features of the human form of MAD.”




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Univ. of Texas Southwestern Medical Center