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Hypercalcitoninaemia in pseudohypo­parathyroidism type 1A and type 1B

Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albrig...

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Autores principales: Yavropoulou, Maria P, Chronopoulos, Efstathios, Trovas, George, Avramidis, Emmanouil, Elli, Francesca Marta, Mantovani, Giovanna, Zebekakis, Pantelis, Yovos, John G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365682/
https://www.ncbi.nlm.nih.gov/pubmed/30703064
http://dx.doi.org/10.1530/EDM-18-0125
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author Yavropoulou, Maria P
Chronopoulos, Efstathios
Trovas, George
Avramidis, Emmanouil
Elli, Francesca Marta
Mantovani, Giovanna
Zebekakis, Pantelis
Yovos, John G
author_facet Yavropoulou, Maria P
Chronopoulos, Efstathios
Trovas, George
Avramidis, Emmanouil
Elli, Francesca Marta
Mantovani, Giovanna
Zebekakis, Pantelis
Yovos, John G
author_sort Yavropoulou, Maria P
collection PubMed
description Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albright hereditary osteodystrophy (AHO). We present two cases, a 54- and a 33-year-old male diagnosed with PHP who were referred to us for persistently high levels of serum calcitonin. AHO and multinodular goitre were present in the 54-year-old male, while the second patient was free of skeletal deformities and his thyroid gland was of normal size and without nodular appearance. We performed GNAS molecular analysis (methylation status and copy number analysis by MS-MLPA) in genomic DNA samples for both patients. The analysis revealed a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1, in the patient with the clinical diagnosis of PHP1A. This amino acid change appears to be in accordance with the clinical diagnosis of the patient. The genomic DNA analysis of the second patient revealed the presence of the recurrent 3-kb deletion affecting the imprinting control region localised in the STX16 region associated with the loss of methylation (LOM) at the GNAS A/B differentially methylated region and consistent with the diagnosis of an autosomal dominant form of PHP type 1B (PHP1B). In conclusion, hypercalcitoninaemia may be encountered in PHP1A and PHP1B even in the absence of thyroid pathology. LEARNING POINTS: We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1 as the cause of PHP1A. Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gsα-mediated hormone signalling. GNAS methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia.
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spelling pubmed-63656822019-02-11 Hypercalcitoninaemia in pseudohypo­parathyroidism type 1A and type 1B Yavropoulou, Maria P Chronopoulos, Efstathios Trovas, George Avramidis, Emmanouil Elli, Francesca Marta Mantovani, Giovanna Zebekakis, Pantelis Yovos, John G Endocrinol Diabetes Metab Case Rep Insight into Disease Pathogenesis or Mechanism of Therapy Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albright hereditary osteodystrophy (AHO). We present two cases, a 54- and a 33-year-old male diagnosed with PHP who were referred to us for persistently high levels of serum calcitonin. AHO and multinodular goitre were present in the 54-year-old male, while the second patient was free of skeletal deformities and his thyroid gland was of normal size and without nodular appearance. We performed GNAS molecular analysis (methylation status and copy number analysis by MS-MLPA) in genomic DNA samples for both patients. The analysis revealed a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1, in the patient with the clinical diagnosis of PHP1A. This amino acid change appears to be in accordance with the clinical diagnosis of the patient. The genomic DNA analysis of the second patient revealed the presence of the recurrent 3-kb deletion affecting the imprinting control region localised in the STX16 region associated with the loss of methylation (LOM) at the GNAS A/B differentially methylated region and consistent with the diagnosis of an autosomal dominant form of PHP type 1B (PHP1B). In conclusion, hypercalcitoninaemia may be encountered in PHP1A and PHP1B even in the absence of thyroid pathology. LEARNING POINTS: We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1 as the cause of PHP1A. Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gsα-mediated hormone signalling. GNAS methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia. Bioscientifica Ltd 2019-01-31 /pmc/articles/PMC6365682/ /pubmed/30703064 http://dx.doi.org/10.1530/EDM-18-0125 Text en © 2018 The authors http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en_GB This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en_GB) .
spellingShingle Insight into Disease Pathogenesis or Mechanism of Therapy
Yavropoulou, Maria P
Chronopoulos, Efstathios
Trovas, George
Avramidis, Emmanouil
Elli, Francesca Marta
Mantovani, Giovanna
Zebekakis, Pantelis
Yovos, John G
Hypercalcitoninaemia in pseudohypo­parathyroidism type 1A and type 1B
title Hypercalcitoninaemia in pseudohypo­parathyroidism type 1A and type 1B
title_full Hypercalcitoninaemia in pseudohypo­parathyroidism type 1A and type 1B
title_fullStr Hypercalcitoninaemia in pseudohypo­parathyroidism type 1A and type 1B
title_full_unstemmed Hypercalcitoninaemia in pseudohypo­parathyroidism type 1A and type 1B
title_short Hypercalcitoninaemia in pseudohypo­parathyroidism type 1A and type 1B
title_sort hypercalcitoninaemia in pseudohypo­parathyroidism type 1a and type 1b
topic Insight into Disease Pathogenesis or Mechanism of Therapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365682/
https://www.ncbi.nlm.nih.gov/pubmed/30703064
http://dx.doi.org/10.1530/EDM-18-0125
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