Analysis of the GCM2 gene in isolated hypoparathyroidism: a molecular and biochemical study

The Journal of Clinical Endocrinology and Metabolism
Alexander MaretMichael A Levine

Abstract

Hypoparathyroidism is characterized by hypocalcemia, hyperphosphatemia, and absent or markedly reduced serum levels of intact PTH. The transcription factor GCM2 is critical for the development of parathyroid glands in mice and humans. We sought to determine the prevalence of GCM2 gene mutations in patients with familial or sporadic forms of isolated hypoparathyroidism (IH). We used PCR to analyze the promoter, the exons, and flanking intronic sequences in 10 IH families with 17 affected members and in 10 patients with sporadic IH. Wild-type and mutant GCM2 proteins were expressed in HEK293 cells and characterized. We identified nine single nucleotide changes, three in the 5' untranslated region and six in exon 5, that led to nonsynonymous changes in the GCM2 protein (G203S, I227V, Y282D, N315D, Q330L, and M354V). Variant GCM2 proteins had normal size, nuclear localization, and transactivational function when expressed in HEK293 cells. Similar analyses of two previously described GCM2 missense mutations, R47L and G63S, revealed decreased nuclear expression and markedly reduced (5-20% of normal) transactivational activity. The variant alleles did not segregate with inheritance of IH, and many of the single nucleotide substitution...Continue Reading

Citations

Jul 29, 2008·Current Opinion in Nephrology and Hypertension·Jeffrey D Zajac, Janine A Danks
May 21, 2010·The Journal of Clinical Investigation·Irina V GrigorievaRajesh V Thakker
Jun 28, 2008·The Journal of Clinical Endocrinology and Metabolism·Michael MannstadtCaroline Silve
Nov 20, 2012·Journal of Pediatric Endocrinology & Metabolism : JPEM·Daniel DoyleMichael A Levine
Apr 17, 2014·Transgenic Research·Ziqiang YuanMichael A Levine
Aug 4, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·John P BilezikianJames Sanders
Jul 9, 2010·Journal of Nursing Management·Kristin Akerjordet, Elisabeth Severinsson
Apr 25, 2015·Ageing Research Reviews·Hao DengJoseph Jankovic
Sep 30, 2016·Frontiers in Physiology·Geoffrey N Hendy, Lucie Canaff
May 14, 2010·The Journal of Clinical Endocrinology and Metabolism·Samantha M MirczukRajesh V Thakker
Mar 9, 2019·The Journal of Clinical Endocrinology and Metabolism·Stephen J Marx
Sep 6, 2019·Journal of Endocrinological Investigation·F CetaniC Marcocci
Aug 17, 2020·International Journal of Molecular Sciences·Marta FigueiredoHélia Neves
Jun 25, 2020·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·An SongXiaoping Xing
Jan 21, 2021·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·An SongXiaoping Xing
Jun 3, 2021·The Journal of Clinical Endocrinology and Metabolism·Priyanka SinghSudhaker Dhanwada Rao
Jun 15, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Elena MarchioriIsabella Merante Boschin
Aug 29, 2021·The Journal of Clinical Endocrinology and Metabolism·Priyanka SinghSudhaker Dhanwada Rao

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.