+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

A missense glial cells missing homolog B (GCMB) mutation, Asn502His, causes autosomal dominant hypoparathyroidism

, : A missense glial cells missing homolog B (GCMB) mutation, Asn502His, causes autosomal dominant hypoparathyroidism. Journal of Clinical Endocrinology and Metabolism 95(7): 3512-3516

Glial cells missing B (GCMB), the mammalian homolog of the Drosophila GCM gene, encodes a 506-amino-acid parathyroid-specific transcription factor. To date, only two different heterozygous GCMB mutations have been reported in three kindreds with autosomal dominant hypoparathyroidism. Our objective was to investigate a family with autosomal dominant hypoparathyroidism for PTH, CaSR, and GCMB mutations. Leukocyte DNA was used with exon-specific primers for PCR amplification and the DNA sequences of the PCR products determined. Functional analyses using fluorescence microscopy, EMSAs, and luciferase reporter assays were undertaken. Informed consent was obtained using protocols approved by a national ethical committee. DNA sequence analysis revealed an A to C transversion at codon 502 of GCMB, which altered the wild-type asparagine (Asn) to histidine (His). Functional studies, using transient transfections of COS7 cells with GCMB wild-type and mutant (Asn502His) tagged constructs, demonstrated that the wild-type and mutant proteins localized to the nucleus and retained the ability to bind the GCM-consensus DNA recognition motif. However, a luciferase reporter assay demonstrated that the Asn502His mutation resulted in a reduction in gene transactivation. Moreover, cotransfection of the wild-type with mutant did not lead to an increase in luciferase activity, thereby demonstrating a dominant-negative effect of the Asn502His mutant that would be consistent with an autosomal dominant inheritance. Our results, which have identified the first dominant missense GCMB mutation, help to increase our understanding of the mechanism underlying gene transactivation that is a prerequisite for the function of this parathyroid gland-specific transcription factor.


PMID: 20463099

DOI: 10.1210/jc.2009-2532

Other references

Anonymous, 1959: Pathophysiology of the kidneys. Die Medizinische 4(27-28): 1322-1323

Layne, C.S.; Mulavara, A.P.; Mcdonald, P.V.; Pruett, C.J.; Kozlovskaya, I.B.; Bloomberg, J.J., 1997: The impact of long duration space flight on upright postural stability during unilateral arm raises. Society for Neuroscience Abstracts 23(1-2): 1562

Chatonnet, P.; Labadie, D.; Boutou, S., 2003: Simultaneous assay of chlorophenols and chloroanisoles in wines and corks or cork-based stoppers. Application in determining the origin of pollution in bottled wines. The contamination of wines and, more rarely, of brandies by corks or cork-based stoppers used as bottles closures has been a recurring issue for many years. The relative frequency of this type of spoilage, characterized by the distinctive, unpleas...

Dolan M.L.; Ove P., 1975: The synthesis of a growth promoting serum factor by rat liver. Journal of Cell Biology 67(2 PART 2): 97A

Thies R., 1990: The use of fresh killed animal organs for student laboratories. FASEB Journal 4(4): A987

Jabeen, F.; Prabhakar, M.; Leelavathi, P., 1991: Foliar architecture in relation to taxonomy of Malvales. Foliar venation in 50 species of Malvales are studied. Some of the venation patterns presently recorded do not fit into any of the patterns earlier described. In order to accommodate them two new terms- palmatous brochidodromous and palmatous acti...

Kapp, O.H.; Polidori, G.; Mainwaring, M.G.; Crewe, A.V.; Vinogradov, S.N., 1984: The reassociation of Lumbricus terrestris hemoglobin dissociated at alkaline pH. The reassociation of the extracellular hemoglobin of Lumbricus terrestris (Mr approximately 3.9 X 10(6) ) at neutral pH, subsequent to its dissociation at pH above 8.0, was examined using gel filtration, ultracentrifugation, and scanning transmiss...

Morrison H.M.; Kramps J.A.; Burnett D.; Stockley R.A., 1986: Measurement of anti elastase function in vitro. Clinical Science (London) 70(SUPPL 13): 28P

Michalska, K.; Szneler, E.; Kisiel, W., 2014: Sesquiterpene lactones from Lactuca canadensis and their chemotaxonomic significance. A total of 19 sesquiterpene lactones were isolated from roots of Lactuca canadensis L., of which 10 were reported for the first time from Lactuca species and two were unknown. This is also the first report on the co-occurrence of three pairs of za...

Narayan, N.P.; Muthusamy, P.; Louis, S.; Ramu, G., 1993: Sample survey of leprosy after three years of MDT in Bhavani taluk of Periyar District, Tamilnadu. A sample survey of Bhavani taluk was undertaken in March 1992 three years after the introduction of MDT. Ten percent of the population was taken for the sample. A population of 45,781 was enumerated and 41,554 was examined. The three sectors were...