Pseudohypoparathyroidism

Linglart, Agnès; Levine, Michael A.; Jüppner, Harald

doi:10.1016/j.ecl.2018.07.011

Cited by 73 publications

(82 citation statements)

References 135 publications

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“…Pseudohypoparathyroidism is a group of disorders associated with endocrine, physical, and neurocognitive abnormalities. 3 Based on the pathogenesis and clinical phenotype, PHP is classified into types Ia-Ic, type II, and pseudo-PHP (PPHP). In most cases, the genetic etiology is a heterozygous inactivating mutation of the GNAS gene or its abnormal methylation.…”

Section: Discussionmentioning

confidence: 99%

Neonatal osteoma cutis due to a mutation in GNAS

Levy‐Shraga

Barel

Javasky

et al. 2019

Pediatric Dermatology

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We describe a 4‐week‐old baby boy who presented with white firm cutaneous nodules and failure to thrive. He did not have dysmorphic features, and laboratory tests including serum calcium, phosphorous, thyroid function, and parathyroid hormone level were within normal ranges. Whole exome sequencing revealed an inactivating mutation in GNAS that was previously described as causing pseudohypoparathyroidism.

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Section: Discussionmentioning

confidence: 99%

Neonatal osteoma cutis due to a mutation in GNAS

Levy‐Shraga

Barel

Javasky

et al. 2019

Pediatric Dermatology

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“…Pseudohypoparathyroidism (PHP) and related disorders have been associated with early-onset obesity (1,2). These diseases, which can present with highly variable clinical findings (3), are caused by a defect in the stimulatory G protein-cAMPsignaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…GNAS is a complex imprinted locus on chromosome 20q13.3. Exons 1-13 encode the alpha-subunit of the stimulatory G protein (Gsα), a signaling protein mediating the functions of several hormones that require the second messenger cAMP down-stream of their cognate receptors (3). GNAS also encodes several other transcripts with incompletely defined biological actions, including the mRNAs encoding the neuroendocrine secretory protein 55 (NESP55) and the extra-large form of Gsα (XLαs), as well as the A/B and the antisense (AS) transcript.…”

Section: Introductionmentioning

confidence: 99%

“…The Gsα transcript is biallelically expressed in most but not all tissues; the paternal expression is reduced in several tissues, e.g., proximal renal tubules, thyroid, gonads, brown adipose tissue, hypothalamus, and pituitary gland (3). Clinical and laboratory manifestations of GNAS mutations are therefore determined by the parental origin of the mutated allele.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, inactivating mutations located on the paternal GNAS allele cause pseudopseudohypoparathyroidism (PPHP) characterized in most patients by several AHO features, but no hormonal resistance, no obesity, and no intellectual challenges. Methylation defects at GNAS exon A/B alone, or at several GNAS DMRs, are observed in pseudohypoparathyroidism type 1B (PHP1B), characterized by resistance to PTH and frequently TSH, but infrequently by AHO features (3).…”

Section: Introductionmentioning

confidence: 99%

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GNAS, PDE4D, and PRKAR1A Mutations and GNAS Methylation Changes Are Not a Common Cause of Isolated Early-Onset Severe Obesity Among Finnish Children

et al. 2020

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Context: Pseudohypoparathyroidism type Ia (PHP1A) is caused by inactivating mutations involving GNAS exons 1-13, encoding the alpha-subunit of the stimulatory G protein (Gsα). Particularly PHP1A, but also other disorders involving the Gsα-cAMPsignaling pathway, have been associated with early-onset obesity. Thus, patients with mutations in the genes encoding PDE4D and PRKAR1A can also be obese. Furthermore, epigenetic GNAS changes, as in pseudohypoparathyroidism type Ib (PHP1B), can lead to excessive weight. Objective: Search for genetic variants in GNAS, PDE4D, and PRKAR1A and for methylation alterations at the GNAS locus in Finnish subjects with isolated severe obesity before age 10 years. Methods: Next generation sequencing to identify pathogenic variants in the coding exons of GNAS, PDE4D, and PRKAR1A; Multiplex Ligation-dependent Probe Amplification (MLPA) and methylation-sensitive MLPA (MS-MLPA) to search for deletions in GNAS and STX16, and for epigenetic changes at the four differentially methylated regions (DMR) within GNAS. Results: Among the 88 subjects (median age 13.8 years, median body mass index Z-score +3.9), we identified one rare heterozygous missense variant of uncertain significance in the XL exon of GNAS in a single patient. We did not identify clearly pathogenic variants in PDE4D and PRKAR1A, and no GNAS methylation changes were detected by MS-MLPA. Conclusions: Our results suggest that coding GNAS mutations or methylation changes at the GNAS DMRs, or coding mutations in PDE4D and PRKAR1A are not common causes of isolated childhood obesity in Finland.

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Parathyroid Gland and Bone Therapies

2023

Endocrinology

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Pseudohypoparathyroidism

Cited by 73 publications

References 135 publications

Neonatal osteoma cutis due to a mutation in GNAS

Neonatal osteoma cutis due to a mutation in GNAS

GNAS, PDE4D, and PRKAR1A Mutations and GNAS Methylation Changes Are Not a Common Cause of Isolated Early-Onset Severe Obesity Among Finnish Children

Parathyroid Gland and Bone Therapies

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