Analysis of Aberrantly Spliced Transcripts of a Novel de novo GNAS Mutant in a Male with Albright Hereditary Osteodystrophy and PHP1A

Ham, Hyoju; Baek, Kwang‐Hyun; Lee, J.-y.; Kim, S. Y.; Mo, Eun Young; Kim, E. S.; Han, Ji-Hye; Moon, Sung Dae

doi:10.1055/s-0034-1395678

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…In patients with PHP1A, the average level of TSH is 14.1 ± 10.3 mUI/1, with a range of 1.4 mUI/1 to 46.0 mUI/1 (REFS 24,30,38,67,98,100,117,119,122,123,129,144–146,149,193–205 ) A prompt diagnosis of hypothyroidism after birth and initiation of treatment does not seem to prevent the development of motor or cognitive delay 24 .…”

Section: Managementmentioning

confidence: 99%

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

et al. 2018

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This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.

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Section: Managementmentioning

confidence: 99%

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

et al. 2018

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“…Since then, several Gsa-coding mutations have been identified in all of its 13 exons with different frequency, with a detection rate of about 70% (33,34,35,36,37,38,39). Cases of deletions of 20q, including part or the whole GNAS gene, and an inversion at GNAS have been recently reported (40,41,42,43,44).…”

Section: Figurementioning

confidence: 99%

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

Thiele

Mantovani

Barlier

et al. 2016

European Journal of Endocrinology

127

124

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Objective: Disorders caused by impairments in the parathyroid hormone (PTH) signalling pathway are historically classified under the term pseudohypoparathyroidism (PHP), which encompasses rare, related and highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and the results of an in vitro assay to measure Gsa protein activity. However, this classification disregards other related diseases such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), as well as recent findings of clinical and genetic/epigenetic background of the different subtypes. Therefore, the EuroPHP network decided to develop a new classification that encompasses all disorders with impairments in PTH and/or PTHrP cAMP-mediated pathway. Design and methods: Extensive review of the literature was performed. Several meetings were organised to discuss about a new, more effective and accurate way to describe disorders caused by abnormalities of the PTH/PTHrP signalling pathway. Results and conclusions: After determining the major and minor criteria to be considered for the diagnosis of these disorders, we proposed to group them under the term 'inactivating PTH/PTHrP signalling disorder' (iPPSD). This terminology: (i) defines the common mechanism responsible for all diseases; (ii) does not require a confirmed genetic defect; (iii) avoids ambiguous terms like 'pseudo' and (iv) eliminates the clinical or molecular overlap

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“…Some of the reported variants are located in the intronic regions near splicing sites. It was shown that these variants frequently lead to the preservation of the mutant intronic sequence in the mRNA [28,29]. In our case, we showed that the identified variant leads to the preservation of the intronic sequence containing a stop codon, which in turn leads to the truncated protein.…”

mentioning

confidence: 49%

A Novel GNAS Mutation in a Patient with Ia Pseudohypoparathyroidism (iPPSD2) Phenotype

Горбачева

Pogoda

Bogdanov

et al. 2023

Genes

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Pseudohypoparathyroidism (PHP) is a heterogeneous orphan disease characterized by multihormonal resistance and several phenotypic features. In some cases, PHP is caused by a mutation in the GNAS that encodes the alpha subunit of the G protein, one of the key transmitters of intracellular signals. A correlation between the genotype and phenotype of patients with GNAS mutations has not yet been described. This often makes diagnosis, drug prescription, and timely diagnosis difficult. Information about GNAS functioning and the impact of specific mutations on the clinical course of the disease is limited. Establishing of the pathogenicity by newly identified GNAS mutations will expand the understanding of this gene functioning in the cAMP signaling pathway and may become the basis for personalized treatment. This paper provides a clinical description of a patient with the Ia PHP phenotype caused by a previously unknown mutation in GNAS (NC_000020.11(NM_000516.7)): c.719-29_719-13delinsACCAAAGAGAGCAAAGCCAAG in the heterozygous state. Verification of the pathogenicity of the detected mutation is also described.

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Analysis of Aberrantly Spliced Transcripts of a Novel de novo GNAS Mutant in a Male with Albright Hereditary Osteodystrophy and PHP1A

Cited by 6 publications

References 21 publications

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

A Novel GNAS Mutation in a Patient with Ia Pseudohypoparathyroidism (iPPSD2) Phenotype

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