ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency

Lian, Jayson; Ćuk, Mario; Kahlfuß, Sascha; Kozhaya, Lina; Vaeth, Martin; Rieux-Laucat, Frédéric; Pïcard, Capucine; Benson, Melina; Jakovčević, Antonia; Bilić, Karmen; Martinac, Iva; Stathopulos, Peter B.; Kacskovıcs, Imre; Vraetz, Thomas; Speckmann, Carsten; Ehl, Stephan; Issekutz, Thomas B.; Unutmaz, Derya; Feske, Stefan

doi:10.1016/j.jaci.2017.10.031

Cited by 78 publications

(72 citation statements)

References 70 publications

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“…These types are categorized as follows: type I) hypoplastic enamel defined by enamel that has reduced thickness (volume); type II) hypomaturation defined by normal thickness but mottled appearance, enamel that chips away from the crown, and radiolucency of enamel similar to dentine; type III) hypocalcified when the thickness is normal but the enamel is poorly calcified as identified by less radiolucency of enamel relative to dentine and its appearance is orange-yellow [29]; type IV) a combination that includes several phenotypes such as hypomaturation-hypoplasia with taurodontism (enlarged pulp chamber). Mutations in the STIM1 and ORAI1 genes reported to date cause enamel defects similar to AI, primarily AI type III [5, 6, 8]. …”

Section: Enamelmentioning

confidence: 99%

“…A recent study by Lian et al [8] identified three novel autosomal recessive mutations in ORAI1 (p.V181SfsX8, p.L194P and p.G98R). All three mutations resulted in abolished expression of ORAI1 as well as SOCE with impaired T-cell function, reduced numbers of Treg cells though invariant natural killer T (iNKT) cells [8].…”

Section: Enamel Defects In Patients With Loss-of-function Mutation Inmentioning

confidence: 99%

“…The same patient had several abscesses and tooth extractions and capped crowns. Patient P3 (p.G98R mutation) was diagnosed with AI type III, supported by oral photographs taken at age 6 that showed severely cracked enamel with exposed dentine although the enamel discoloration seen in other patients is not apparent [8]. …”

Section: Enamel Defects In Patients With Loss-of-function Mutation Inmentioning

confidence: 99%

“…Patients with mutations in STIM1 and ORAI1 have been described as presenting with ectodermal dysplasia (ED), given that they show phenotypes that are similar to those in ED patients [6–8, 56, 57]. ED are a group of heterogeneous, heritable conditions associated with the abnormal development of ectoderm-derived structures and associated appendages [58].…”

Section: Crac Channels and Ectodermal Dysplasiamentioning

confidence: 99%

“…Presently, there is no clear evidence that STIM1 or ORAI1 are critical mediators in the morphogenesis of ectodermderived structures. In fact, from the available published data, it has been recognized that the morphogenesis of two ectodermal structures, sweat glands and teeth, is unaffected by mutations in ORAI1 or STIM1 in humans, or in animal models lacking either of these genes [8, 11, 54]. The impact of CRAC channel deficiency is, however, critical for the normal function of the developed tissues.…”

Section: Crac Channels and Ectodermal Dysplasiamentioning

confidence: 99%

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CRAC channels in dental enamel cells

Eckstein

Lacruz

2018

Cell Calcium

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Enamel mineralization relies on Ca availability provided by Ca release activated Ca (CRAC) channels. CRAC channels are modulated by the endoplasmic reticulum Ca sensor STIM1 which gates the pore subunit of the channel known as ORAI1, found the in plasma membrane, to enable sustained Ca influx. Mutations in the STIM1 and ORAI1 genes result in CRAC channelopathy, an ensemble of diseases including immunodeficiency, muscular hypotonia, ectodermal dysplasia with defects in sweat gland function and abnormal enamel mineralization similar to amelogenesis imperfecta (AI). In some reports, the chief medical complain has been the patient's dental health, highlighting the direct and important link between CRAC channels and enamel. The reported enamel defects are apparent in both the deciduous and in permanent teeth and often require extensive dental treatment to provide the patient with a functional dentition. Among the dental phenotypes observed in the patients, discoloration, increased wear, hypoplasias (thinning of enamel) and chipping has been reported. These findings are not universal in all patients. Here we review the mutations in STIM1 and ORAI1 causing AI-like phenotype, and evaluate the enamel defects in CRAC channel deficient mice. We also provide a brief overview of the role of CRAC channels in other mineralizing systems such as dentine and bone.

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Section: Enamelmentioning

confidence: 99%

Section: Enamel Defects In Patients With Loss-of-function Mutation Inmentioning

confidence: 99%

Section: Enamel Defects In Patients With Loss-of-function Mutation Inmentioning

confidence: 99%

Section: Crac Channels and Ectodermal Dysplasiamentioning

confidence: 99%

Section: Crac Channels and Ectodermal Dysplasiamentioning

confidence: 99%

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CRAC channels in dental enamel cells

Eckstein

Lacruz

2018

Cell Calcium

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Combined Immunodeficiencies

Rubin,

Williams,

Lawrence

2024

Manual of Molecular and Clinical Laboratory Immunology

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Prussian Blue‐Derived Nanocomposite Synergized with Calcium Overload for Three‐Mode ROS Outbreak Generation to Enhance Oncotherapy

Xu,

Zhou,

et al. 2024

Adv Healthcare Materials

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Calcium overload can lead to tumor cell death. However, because of the powerful calcium channel excretory system within tumor cells, simplistic calcium overloads do not allow for an effective antitumor therapy. Hence, the nanoparticles are created with polyethylene glycol (PEG) donor‐modified calcium phosphate (CaP)‐coated, manganese‐doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP‐PEG (GMCP). GMCP with a three‐mode enhancement of intratumor reactive oxygen species (ROS) levels is designed to increase the efficiency of the intracellular calcium overload in tumor cells to enhance its anticancer efficacy. The released exogenous Ca2+ and the production of cytotoxic ROS resulting from the perfect circulation of the three‐mode ROS outbreak generation that Fenton/Fenton‐like reaction and consumption of glutathione from Fe2+/Fe3+and Mn2+/Mn3+ circle, and amelioration of hypoxia from MMPB‐guided and GOx‐mediated starvation therapy. Photothermal efficacy‐induced heat generation owing to MMPB accelerates the above reactions. Furthermore, abundant ROS contribute to damage to mitochondria, and the calcium channels of efflux Ca2+ are inhibited, resulting in a calcium overload. Calcium overload further increases ROS levels and promotes apoptosis of tumor cells to achieve excellent therapy.

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ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency

Cited by 78 publications

References 70 publications

CRAC channels in dental enamel cells

CRAC channels in dental enamel cells

Combined Immunodeficiencies

Prussian Blue‐Derived Nanocomposite Synergized with Calcium Overload for Three‐Mode ROS Outbreak Generation to Enhance Oncotherapy

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