Calcium-Sensing Receptor Autoantibodies Are Relevant Markers of Acquired Hypoparathyroidism

Mayer, Anne E.; Ploix, Corinne; Orgiazzi, Jacques; Desbos, Agnès; Moreira, Annick; Vidal, Hubert; Monier, J. C.; Bienvenu, Jacques; Fabien, Nicole

doi:10.1210/jc.2004-0021

Cited by 67 publications

(44 citation statements)

References 18 publications

(17 reference statements)

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“…Hypoparathyroidism is a heterogeneous group of disorders characterized by tetany, cataract, basal ganglia calcification, hypocalcemia, hyperphosphatemia, and subnormal serum parathyroid hormone (PTH) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Recently, Dolores Shoback has classified its pathophysiologic mechanisms into three broad categories (13).…”

Section: Introductionmentioning

confidence: 99%

“…Patients with isolated hypoparathyroidism (IH) also referred to as acquired or idiopathic hypoparathyroidism demonstrate the presence of CaSR autoantibodies with prevalence varying from 29 to 56% (10)(11)(12). However, they do not demonstrate increased risk of coexisting thyroid autoimmunity unlike in type-1 diabetes and premature ovarian failure (14).…”

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: 99%

Section: Introductionmentioning

confidence: 99%

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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“…It occurs after thyroid or parathyroid surgery, if all parathyroid tissue is removed; as a consequence of autoimmune disorders, such as antibodies that activate the calcium sensing receptor of the parathyroid glands (1)(2)(3) ; and, more rarely, as a congenital disorder of parathyroid dysgenesis, such as DiGeorge syndrome. (4)(5)(6)(7) Independent of etiology, the typical biochemical constellation in untreated hypoparathyroidism includes low circulating PTH levels, hypocalcemia, relatively high urinary calcium excretion, hyperphosphatemia, and reduced levels of 1,25-dihydroxyvitamin D. (8,9) In the absence of PTH, bone remodeling is reduced.…”

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confidence: 99%

Dynamic and Structural Properties of the Skeleton in Hypoparathyroidism

Rubin¹,

Dempster²,

Zhou³

et al. 2008

Journal of Bone and Mineral Research

180

139

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Hypoparathyroidism, a disorder in which PTH is absent, is associated with BMD that is above average. We studied associated structural and dynamic properties of the skeleton in hypoparathyroidism. Thirty-three subjects with hypoparathyroidism and 33 age-and sex-matched control subjects with no known metabolic diseases underwent percutaneous iliac crest bone biopsies after double-labeling with tetracycline. The main outcome was histomorphometric assessment of structural and dynamic skeletal parameters. Subjects with hypoparathyroidism had greater cancellous bone volume (mean ± SD; BV/TV: 23.5 ± 8 versus 19.7 ± 5%, p ‫ס‬ 0.02), trabecular width (Tb.Wi: 136.1 ± 37 versus 119.3 ± 21 m, p ‫ס‬ 0.03), and cortical width (Ct.Wi: 923.4 ± 420 versus 753.5 ± 246 m, p ‫ס‬ 0.05) than control subjects. Dynamic skeletal indices, including mineralizing surface (MS: 0.85 ± 1.58 versus 4.27 ± 3.32%, p < 0.0001) and bone formation rate (BFR/BS: 0.006 ± 0.014 versus 0.032 ± 0.028 m 3 /m 2 /d, p < 0.0001), were profoundly suppressed in the hypoparathyroid subjects. We conclude that hypoparathyroidism is characterized by markedly unusual structural and dynamic properties of bone.

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“…Disor (4)(5)(6). Considering autoimmune hypoparathyroidism, the role of anti-calcium sensor autoimmunity has been challenged (7), but it has also been shown that detection of antibodies against the receptor is influenced by the assay system used (6).…”

Section: Diseases Associated With the Calcium-sensing Receptor Includmentioning

confidence: 99%

Hyperparathyroidism in a Patient with Autoimmune Polyglandular Syndrome

et al. 2008

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Calcium-Sensing Receptor Autoantibodies Are Relevant Markers of Acquired Hypoparathyroidism

Cited by 67 publications

References 18 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

Dynamic and Structural Properties of the Skeleton in Hypoparathyroidism

Hyperparathyroidism in a Patient with Autoimmune Polyglandular Syndrome

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