Disease relevance of GCM2

• Finally, intrathymic PTH-secreting adenomas express the parathyroid-specific GCMB gene, which suggests that these tumors were derived from parathyroid cells that migrated errantly during embryogenesis [1].
• 2. Transcripts of GCMB were detected by means of RT-PCR in fetal brain, normal adult kidney, 3/3 medulloblastomas, 1/3 gliomas and 4/8 non-neuroepithelial tumor cell lines [2].
• There was no difference in the level of GCMB mRNA expression between parathyroid adenoma, hyperplasia, and cancer [3].
• RESULTS: We found high Gcm2 mRNA expression in human parathyroid glands in comparison with other non-neural tissues and underexpression in parathyroid adenomas but not in lesions of HPT secondary to uraemia [4].
• CONCLUSIONS: GCMB expression is upregulated in abnormal parathyroid glands of hyperparathyroidism and decreases in response to hypocalcemia [3].

High impact information on GCM2

• We conclude that homozygous loss of function of the GCMB gene impairs normal parathyroid gland embryology and is responsible for isolated hypoparathyroidism in a subset of patients with this disease [5].
• We defined the boundaries of the five exons of the human GCMB gene and then identified a large intragenic mutation in the GCMB genes of the proband of an extensive kindred with isolated hypoparathyroidism [5].
• Despite an absence of any history of consanguinity, microsatellite analysis showed shared genotypes that flanked the GCMB gene over a span of 5 cM, suggesting that both of the proband's GCMB alleles had been derived from a single common ancestor [5].
• Functional studies in transfected cells showed that the mutation caused loss of GCMB function, as it abolished transactivation capacity, despite normal subcellular localization, protein stability, and DNA-binding specificity [6].
• The mutation consisted of the substitution of a glycine residue with a serine at position 63 (G63S) in the DNA-binding GCM domain of GCMB [6].

Biological context of GCM2

• Homology searches indicated that GCMB was located within chromosome 6p24 [2].

Anatomical context of GCM2

• GCMA and GCMB are related transcription factors that are critically important for embryological development of the placenta and parathyroid glands, respectively [1].
• A novel human homologue (GCMB) of the Drosophila glial cells missing gene (dGCM) was isolated using RACE [2].
• Using organ-specific markers, we have previously shown that thymus and parathyroid-specific organ domains are established within the primordium prior to formation of the organs proper: Gcm2 expression defines the prospective parathyroid cells in the dorsal pouch from E9.5, while Foxn1 is expressed in the thymus domain from E11.25 [7].

Other interactions of GCM2

• Identification of a novel mutation disrupting the DNA binding activity of GCM2 in autosomal recessive familial isolated hypoparathyroidism [8].
• Mice in which parathyroid glands have been surgically removed or fail to develop due to genetic loss of GCMB show continued production of PTH from a subset of thymic cells that express GCMA [1].
• We postulated that the GCMB gene might play a role in parathyroid tumorigenesis in hyperparathyroidism [3].
• METHODS: We used real-time quantitative reverse transcriptase polymerase chain reaction to study GCMB mRNA expression in parathyroid tissue: normal (n = 3), hyperplastic (n = 16), adenomas (n = 19), and cancers (n = 8) [3].
• Here, we describe a 34-year-old patient with myasthenia gravis who presented with GCM 2 weeks after resection of a thymoma [9].

Analytical, diagnostic and therapeutic context of GCM2

• In primary parathyroid culture, the effect of CaCl 2 on parathyroid hormone secretion and GCMB mRNA expression was studied by using enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction, respectively [3].

References