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A novel deletion involving the first GNAS exon encoding Gsα causes PHP1A without methylation changes at exon A/B

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dc.contributor.authorBEREKET, ABDULLAH
dc.contributor.authorDEMİRCİOĞLU, SERAP
dc.contributor.authorGÜRAN, TÜLAY
dc.contributor.authorsCampbell D., Reyes M., Kaygusuz S. B., Abalı S., Güran T., Bereket A., Kagami M., Turan S., Jüppner H.
dc.date.accessioned2023-03-06T08:08:59Z
dc.date.available2023-03-06T08:08:59Z
dc.date.issued2022-04-01
dc.description.abstract© 2022Individuals affected by pseudohypoparathyroidism type 1A (PHP1A) display hyperphosphatemia and hypocalcemia despite elevated PTH levels, as well as features of Albright Hereditary Osteodystrophy (AHO). PHP1A is caused by variants involving the maternal GNAS exons 1–13 encoding the stimulatory G protein α-subunit (Gsα). MLPA and aCGH analysis led in a male PHP1A patient to identification of a de novo 1284-bp deletion involving GNAS exon 1. This novel variant overlaps with a previously identified 1438-bp deletion in another PHP1A patient (ref. Li et al. (2020) [13], patient 2) that extends from the exon 1 promoter into the up-stream intronic region. This latter deletion is associated with reduced methylation at GNAS exon A/B, i.e. the differentially methylated region (DMR) that is demethylated in most pseudohypoparathyroidism type 1B (PHP1B) patients. In contrast, genomic DNA from our patient revealed no evidence for an epigenetic GNAS defect as determined by MS-MLPA and pyrosequencing. These findings thus reduce the region, which, in addition to other nucleotide sequences telomeric of exon A/B, may undergo histone modifications or interacts with transcription factors and possibly as-yet unknown proteins that are required for establishing the maternal methylation imprints at this site. Taken together, nucleotide deletions or changes within an approximately 1300-bp region telomeric of exon A/B could be a cause of PHP1B variants with complete or incomplete loss-of-methylation at the exon A/B DMR. In addition, when investigating patients with suspected PHP1A, MLPA should be considered to search for structural abnormalities within this difficult to analyze genomic region comprising GNAS exon 1.
dc.identifier.citationCampbell D., Reyes M., Kaygusuz S. B., Abalı S., Güran T., Bereket A., Kagami M., Turan S., Jüppner H., "A novel deletion involving the first GNAS exon encoding Gsα causes PHP1A without methylation changes at exon A/B", Bone, cilt.157, 2022
dc.identifier.doi10.1016/j.bone.2022.116344
dc.identifier.issn8756-3282
dc.identifier.urihttps://hdl.handle.net/11424/287115
dc.identifier.volume157
dc.language.isoeng
dc.relation.ispartofBone
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectTıp
dc.subjectSağlık Bilimleri
dc.subjectDahili Tıp Bilimleri
dc.subjectÇocuk Sağlığı ve Hastalıkları
dc.subjectPediatrik Endokrinoloji ve Metabolizma
dc.subjectMedicine
dc.subjectHealth Sciences
dc.subjectInternal Medicine Sciences
dc.subjectChild Health and Diseases
dc.subjectPediatric Endocrinology and Metabolism
dc.subjectKlinik Tıp (MED)
dc.subjectKlinik Tıp
dc.subjectTIP, GENEL & DAHİLİ
dc.subjectPEDİATRİ
dc.subjectClinical Medicine (MED)
dc.subjectCLINICAL MEDICINE
dc.subjectMEDICINE, GENERAL & INTERNAL
dc.subjectPEDIATRICS
dc.subjectPediatrics
dc.subjectFamily Practice
dc.subjectFundamentals and Skills
dc.subjectGeneral Health Professions
dc.subjectPathophysiology
dc.subjectPediatrics, Perinatology and Child Health
dc.subjectInternal Medicine
dc.subjectAssessment and Diagnosis
dc.subjectMedicine (miscellaneous)
dc.subjectGeneral Medicine
dc.subjectPseudohypoparathyroidism type Ia (PHP1A)
dc.subjectAlbright hereditary osteodystrophy
dc.subjectParathyroid hormone
dc.subjectCalcium
dc.subjectPhosphate
dc.subjectGs-alpha
dc.subjectGs alpha
dc.subjectEpigenetics
dc.subjectGNAS methylation
dc.subjectPSEUDOHYPOPARATHYROIDISM
dc.subjectPROTEIN
dc.subjectCYCLASE
dc.subjectGENE
dc.subjectGsα
dc.titleA novel deletion involving the first GNAS exon encoding Gsα causes PHP1A without methylation changes at exon A/B
dc.typearticle
dspace.entity.typePublication
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local.indexed.atWOS
local.indexed.atPUBMED
local.indexed.atSCOPUS
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relation.isAuthorOfPublicationcd5bac46-bf24-476a-80cb-1cea576c283a
relation.isAuthorOfPublication.latestForDiscovery669e9474-4e39-453f-a4bc-4ede9cb5abac

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