Analysis of the<i>GCM2</i>Gene in Isolated Hypoparathyroidism: A Molecular and Biochemical Study

Maret, Alexander; Ding, Changlin; Kornfield, Sara L.; Levine, Michael A.

doi:10.1210/jc.2007-1783

Cited by 44 publications

(35 citation statements)

References 38 publications

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“…GCM2 gene sequence was normal in them (22,25). We report GCM2 gene sequence analysis in a large cohort of patients with IH (14,(18)(19)(20)(21) and report occurrence of a new R110W mutation and its functional significance.…”

Section: Introductionmentioning

confidence: 80%

“…The first and last 12 patients (17 males) were selected for complete sequencing of the GCM2 gene, which included all its the five exons, intron-exon boundaries, and 5 0 and 3 0 UTRs. The 5 0 upstream sequence up to K652 position from translation start site ATG included 5 0 UTR of exon 1, promoter sequence, and binding sites for PAX1 and PAX9 transcription factors (25).…”

Section: Patientsmentioning

confidence: 99%

“…Although there are six reports of GCM2 gene analysis in patients with familial hypoparathyroidism, only two included a total of 20 patients with IH (22,25). GCM2 gene sequence was normal in them (22,25).…”

Section: Introductionmentioning

confidence: 98%

“…Recently, familial hypoparathyroidism has also been linked with mutations of GCM gene (22)(23)(24)(25)(26)(27). The GCM gene encodes a glial cells-specific transcription factor in Drosophila (28) and its mammalian homologs, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…gcm1 and gcm2 (mouse) and GCM1 and GCM2 (humans) encode transcription factors necessary for the development of placenta and parathyroid glands in the fetus and adults respectively (29)(30)(31). The GCM2 gene located on chromosome 6p23-24 encodes a 506 amino acids protein with DNA-binding domain from 21 to 174 amino acids, and its response elements have been described in the CASR gene (25,27,32).…”

Section: Introductionmentioning

confidence: 99%

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Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members

Tomar¹,

Bora²,

Singh³

et al. 2010

European Journal of Endocrinology

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Objective: Glial cells missing 2 (GCM2) gene encodes a parathyroid-specific transcription factor. We assessed GCM2 gene sequence in patients with isolated hypoparathyroidism (IH). Design: Case-control study. Methods: Complete DNA sequencing of the GCM2 gene including its exons, promoter, and 5 0 and 3 0UTRs was performed in 24/101 patients with IH. PCR-restriction fragment length polymorphism was used to detect a novel R110W mutation in all 101 IH patients and 655 healthy controls. Significance of the mutation was assessed by electrophoretic mobility shift assay (EMSA) and nuclear localization on transfection.Results: A heterozygous R110W mutation was present in DNA-binding domain in 11/101 patients (10.9%) and absent in 655 controls (P!10 K7 ). Four of 13 nonaffected first-degree relatives for five of these index cases had R110W mutation. Four heterozygous single nucleotide polymorphisms were found in the 5 0 region. One of the 11 patients with R110W also had T370M change in compound heterozygous form. Mutant R110W and T370M GCM2 proteins showed decreased binding with GCM recognition elements on EMSA indicating loss of function. Both wild-type and R110W mutant GCM2 proteins showed nuclear localization. Conclusions: The present study indicates a significant association of R110W variant with IH. Absence of effect of heterozygous R110W mutation on DNA binding and presence of the same mutation in asymptomatic family members indicate that additional genetic (akin to T370M change) or nongenetic factors might contribute to the expression of diseases in IH. Alternatively, it is possible that association of R110W with IH could be due to linkage disequilibrium with the unidentified relevant genes in IH.

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Section: Introductionmentioning

confidence: 80%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members

Tomar¹,

Bora²,

Singh³

et al. 2010

European Journal of Endocrinology

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The Parathyroid and Disorders of Calcium and Bone Metabolism

Allgrove

Frcp²,

Consultant³

2009

Brook's Clinical Pediatric Endocrinology

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Hypoparathyroidism in the adult: Epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research

Bilezikian¹,

Khan²,

Potts³

et al. 2011

Journal of Bone and Mineral Research

516

435

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Recent advances in understanding the epidemiology, genetics, diagnosis, clinical presentations, skeletal involvement, and therapeutic approaches to hypoparathyroidism led to the First International Workshop on Hypoparathyroidism that was held in 2009. At this conference, a group of experts convened to discuss these issues with a view towards a future research agenda for this disease. This review, which focuses primarily on hypoparathyroidism in the adult, provides a comprehensive summary of the latest information on this disease. © 2011 American Society for Bone and Mineral Research

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Analysis of theGCM2Gene in Isolated Hypoparathyroidism: A Molecular and Biochemical Study

Abstract: Our study describes nine single nucleotide changes in the GCM2 gene that represent polymorphisms. Although GCM2 mutations appear to be an uncommon cause of IH, the wide variety of GCM2 polymorphisms suggests that variant alleles may have a role in determining parathyroid function.

Cited by 44 publications

References 38 publications

Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members

Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members

The Parathyroid and Disorders of Calcium and Bone Metabolism

Hypoparathyroidism in the adult: Epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research

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