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Tanpakushitsu Kakusan Koso. Protein,... Apr 1988
Topics: Cyclic AMP; GTP-Binding Proteins; Humans; Pseudohypoparathyroidism
PubMed: 2855957
DOI: No ID Found -
Journal of Pediatric Endocrinology &... Mar 2003Gain or loss of function mutations of the GNAS1 gene lead to McCune-Albright syndrome (MAS) or pseudohypoparathyroidism Ia (PHP-Ia), respectively. Patients with MAS,... (Review)
Review
Gain or loss of function mutations of the GNAS1 gene lead to McCune-Albright syndrome (MAS) or pseudohypoparathyroidism Ia (PHP-Ia), respectively. Patients with MAS, caused by a post-zygotic missense mutation leading to constitutive activation of Gs alpha, suffer from gonadotropin-independent precocious puberty, and delayed or incomplete sexual development and reproductive dysfunction is found in women with PHP-Ia, an inherited disorder caused by deficient expression or function of the Gs alpha protein. In females with MAS, 50% developed precocious puberty by the age of 4 years, the remaining between 4 and 8 years. Peripheral precocious puberty is often atypical and characterized by alternate periods of rapid progression and regression of pubertal development; menstrual bleeding may occur before breast development. Ovarian cyst growth and regression is often described as a sign of ovarian follicle hyperactivation. Notwithstanding this clinical heterogeneity, a subset of patients with MAS develop relentlessly progressive precocious puberty ultimately resulting in premature epiphyseal fusion and reduced adult stature. Long-term information on reproductive function has been obtained in females: some patients had regular menses without ovarian cysts on pelvic US scan, whereas others were oligomenorrheic and showed recurrent ovarian cysts. In males with MAS, precocious puberty occurred in three patients between 4 and 9 years of age. In one patient, long-term follow-up demonstrated normal plasma testosterone and gonadotropin values at the age of 17 years. On testicular sonography, multiple hyperechogeneic spots were found in both testicles (snow-storm appearance). Female patients with PHP-Ia were oligomenorrheic or amenorrheic; more than half had delayed or incomplete sexual development, They were mildly hypoestrogenic with normal to slightly elevated serum gonadotropin levels. These clinical and biochemical findings indicate partial resistance of the theca and granulosa cells of the ovary to gonadotropins due to deficient Gs alpha activity. Responsiveness might be sufficient to promote some degree of follicular development and steroid secretion, but insufficient to induce ovulation
Topics: Amenorrhea; Female; Fibrous Dysplasia, Polyostotic; Humans; Pseudohypoparathyroidism; Puberty; Puberty, Precocious
PubMed: 12729407
DOI: No ID Found -
Journal of Pediatric Endocrinology &... May 2006
Topics: Chromosomes, Human, Pair 20; Fibrous Dysplasia, Polyostotic; GTP-Binding Protein alpha Subunits, Gs; Gene Deletion; History, 20th Century; History, 21st Century; Humans; Mutation; Pseudohypoparathyroidism
PubMed: 16789627
DOI: 10.1515/jpem.2006.19.s2.627 -
Endocrinologia, Diabetes Y Nutricion Oct 2018
Topics: Consensus Development Conferences as Topic; Humans; International Cooperation; Pseudohypoparathyroidism
PubMed: 30243379
DOI: 10.1016/j.endinu.2018.08.002 -
Annales D'endocrinologie Dec 2022
Topics: Humans; Hypokalemia; Pseudohypoparathyroidism; DNA Methylation; GTP-Binding Protein alpha Subunits, Gs; Chromogranins
PubMed: 36371350
DOI: 10.1016/j.ando.2022.09.022 -
Tidsskrift For Den Norske Laegeforening... May 1987
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Pseudohypoparathyroidism
PubMed: 3603486
DOI: No ID Found -
Odontostomatologike Proodos 1981
Topics: Child; Humans; Male; Pseudohypoparathyroidism; Tooth Diseases
PubMed: 6801565
DOI: No ID Found -
Hormone and Metabolic Research =... Sep 2012Pseudohypoparathyroidism-Ia and -Ib (PHP-Ia and -Ib) are caused by mutations in GNAS exons 1-13 and methylation defects in the imprinted GNAS cluster, respectively.... (Review)
Review
Pseudohypoparathyroidism-Ia and -Ib (PHP-Ia and -Ib) are caused by mutations in GNAS exons 1-13 and methylation defects in the imprinted GNAS cluster, respectively. PHP-Ia patients show Albright hereditary osteodystrophy (AHO), together with resistance to the action of different hormones that activate the Gs-coupled pathway. In PHP-Ib patients AHO is classically absent and hormone resistance is limited to PTH and TSH. This disorder is caused by GNAS methylation alterations with loss of imprinting at the exon A/B differentially methylated region (DMR) being the most consistent and recurrent defect. The familial form of the disease (AD-PHP-Ib) is typically associated with an isolated loss of imprinting at the exon A/B DMR due to microdeletions disrupting the upstream STX16 gene. In addition, deletions removing the entire NESP55 DMR, located within GNAS, associated with loss of all the maternal GNAS imprints have been identified in some AD-PHP-Ib kindreds. Conversely, most sporadic PHP-Ib cases have GNAS imprinting abnormalities that involve multiple DMRs, but the genetic lesion underlying these defects is unknown. Recently, methylation defects have been detected in a subset of patients with PHP-Ia and variable degrees of AHO, indicating a molecular overlap between the 2 forms. Imprinting defects do not seem to be associated with the severity of AHO neither with specific AHO signs. In conclusion, the latest findings on the molecular basis underlying these defects suggest the existence of a clinical and genetic/epigenetic overlap between PHP-Ia and PHP-Ib, and highlight the necessity of a new clinical classification of these disorders based on molecular findings.
Topics: Chromogranins; Epigenesis, Genetic; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation; Parathyroid Hormone; Pseudohypoparathyroidism
PubMed: 22674477
DOI: 10.1055/s-0032-1314842 -
Clinical Endocrinology Jun 2016Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GNAS complex locus. It is characterized by target organ resistance to PTH,...
OBJECTIVE
Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GNAS complex locus. It is characterized by target organ resistance to PTH, resulting in hypocalcaemia and hyperphosphataemia. Studies in patients with PHP are limited. We sought to identify all patients in Denmark with PHP and access their mortality data and risk of complications.
DESIGN
Patients were identified through the Danish National Patient Registry and a prescription database, with subsequent validation by investigation of patient charts.
METHODS
For each case, three age- (±2 years) and gender-matched controls were randomly selected from the general background population. We identified a total of 60 cases, equal to a prevalence of 1·1/100 000 inhabitants. The average age at diagnosis was 13 years (range 1-62 years), and 42 were women. Only 14 patients had an identified mutation in the GNAS1 gene.
RESULTS
Compared with controls, patients with PHP had an increased risk of neuropsychiatric disorders (P < 0·01), infections (P < 0·01), seizures (P < 0·01) and cataract (P < 0·01), whereas their risk of renal, cardiovascular, malignant disorders and fractures was compatible with the general background population. The same tendencies were found in a subgroup analysis in cases with genetically verified PHP.
CONCLUSION
Patients with PHP have an increased risk of neuropsychiatric disorders, infections, cataract and seizures, whereas mortality among PHP patients is compatible with that in the background population.
Topics: Adolescent; Adult; Case-Control Studies; Cataract; Child; Child, Preschool; Chromogranins; Denmark; Female; GTP-Binding Protein alpha Subunits, Gs; Humans; Infant; Infections; Male; Mental Disorders; Middle Aged; Mutation; Pseudohypoparathyroidism; Seizures; Young Adult
PubMed: 26387561
DOI: 10.1111/cen.12948 -
Internal Medicine (Tokyo, Japan) 2014We herein describe the case of a woman with pseudohypoparathyroidism (PHP) type II. She had a history of subtotal thyroidectomy against Graves' disease without...
We herein describe the case of a woman with pseudohypoparathyroidism (PHP) type II. She had a history of subtotal thyroidectomy against Graves' disease without levothyroxine supplementation and presented with stiffness, numbness and muscle cramps. Her surgical history suggested the possibility of secondary hypoparathyroidism; however, the serum intact parathyroid hormone level and results of a Ellsworth-Howard test led to the diagnosis of PHP type II. In the present case, making the differential diagnosis was challenging because two distinct disorders, such as PHP and secondary hypoparathyroidism, may exist simultaneously. This case demonstrates the need to consider the possibility of PHP type II in patients exhibiting hypocalcemia.
Topics: Aged; Diagnosis, Differential; Female; Graves Disease; Humans; Parathyroid Hormone; Pseudohypoparathyroidism; Thyroidectomy
PubMed: 24694489
DOI: 10.2169/internalmedicine.53.1617