|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Heterozygous inactivating mutations involving the maternal GNAS exons 1-13 that encodes the alpha subunit of the stimulatory G protein (Gsα) cause inactivating parathyroid hormone (PTH)/PTHrP signalling disorder type 2 (iPPSD2 or PHP type 1A), which is characterized by Albright hereditary osteodystrophy and resistance to multiple hormones that act through the Gsα signalling pathway (including PTH, thyroid-stimulating hormone, and α-melanocyte-stimulating hormone).
|
31696922 |
2019 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
Biomarker
|
disease |
BEFREE |
An AHO-like phenotype was associated with the loss of genetic information stored in chromosome 2q37, making this genomic region an interesting object of study as it could contain modifier genes involved in the development of AHO features in patients with GNAS imprinting defects.
|
30616679 |
2019 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Inactivating mutations in Gsα-coding GNAS exons are responsible for Albright's hereditary osteodystrophy (AHO), which refers to a constellation of physical and developmental disorders including obesity, short stature, brachydactyly, cognitive impairment, and heterotopic ossification.
|
28889026 |
2018 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
With respect to mosaic conditions, the study of multiple tissues is a necessary approach; thus, we investigated somatic cell lines (peripheral blood and buccal epithelium and cells from the urine sediment) descending from different germ layers from 19 PHP patients (11 spor-PHP1B, 4 GNAS mutated PHP1A, and 4 PHP with no GNAS (epi)genetic defects) and 5 healthy controls.
|
29445425 |
2018 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Screening for GNAS mutations should be considered in suspected cases of PHP1A even if the classical signs are not present.
|
30060753 |
2018 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Early-onset obesity characterizes GNAS alterations and is associated with significant overweight and obesity in adults (bodey mass index [BMI] Z-score: 1.4 ± 2.6, 2.1 ± 2.0, and 1.4 ± 1.9 in PPHP, PHP1A, and PHP1B, respectively), indicating that reduced Gsα expression is a contributing factor.
|
29693731 |
2018 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
We evaluated 67 patients with AHO (49 with PHP1A, 18 with PPHP) with documented mutations in GNAS.
|
29059381 |
2018 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus.
|
29499646 |
2018 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Similarly, impressive early weight gains were noted in five patients, who initially lacked additional Albright hereditary osteodystrophy features but in whom PHP1A due to GNAS mutations involving exons encoding Gsα was diagnosed.
|
28453643 |
2017 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Heterozygous inactivating mutations involving the maternal GNAS exons 1-13 cause PHP type Ia (PHP1A).
|
27995443 |
2017 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Similarly, impressive early weight gains were noted in five patients, who initially lacked additional Albright hereditary osteodystrophy features but in whom PHP1A due to GNAS mutations involving exons encoding Gsα was diagnosed.
|
28453643 |
2017 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Here, we report a de novo 50-bp tandem duplication in GNAS (c.723_772dup50, p.Glu259Leufs*29) identified in a patient with typical clinical features of PHP1a.
|
29320763 |
2017 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
A maternally inherited 2015-bp deletion that includes GNAS exon 1 was identified thereby establishing the diagnosis of PHP1A.
|
28711660 |
2017 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Pseudohypoparathyroidism type Ia (PHP1A) or type Ib (PHP1B) are caused by heterozygous maternal GNAS mutations suggesting that little or no Gαs is derived in some tissues from the non-mutated paternal GNAS thereby causing hormonal resistance.
|
28694163 |
2017 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
CausalMutation
|
disease |
CLINVAR |
Molecular diagnostic experience of whole-exome sequencing in adult patients.
|
26633545 |
2016 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
A novel mutation in a case of pseudohypoparathyroidism type Ia.
|
27922245 |
2016 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
Biomarker
|
disease |
BEFREE |
Epigenetic changes in GNAS have also been reported in patients who display mild Albright's hereditary osteodystrophy or mild thyroid-stimulating hormone (TSH) resistance without mutation of GNAS.
|
25802348 |
2015 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
This report adds to rare publications describing constitutional aberrations of chromosome 20q, and adds further evidence to the fact that deletion of the GNAS complex may not always be associated with an Albright's hereditary osteodystrophy phenotype as described previously.
|
25761574 |
2015 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
CausalMutation
|
disease |
CLINVAR |
A positive genotype-phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo-pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene.
|
25802881 |
2015 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
We observed that deletions at GNAS locus represent a significant cause of PPHP/PHP1A and that such defects are mostly associated with Alu-mediated recombination events.
|
25594858 |
2015 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
PosttranslationalModification
|
disease |
BEFREE |
Microdeletions that alter GNAS methylation and, thereby, diminish Gsα expression in tissues in which the paternal Gsα allele is normally silenced also cause hormone resistance, which occurs typically in the absence of AHO, a disorder termed pseudohypoparathyroidism type-Ib.
|
25851935 |
2015 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Hypothyroidism is a particular condition observed in pseudohypoparathyroidism (PHP), a rare disorder characterized by parathyroid (PTH) resistance leading to hypocalcemia and hyperphosphatemia associated with a GNAS (guanine nucleotide-binding protein α-subunit) mutation (PHP1A) or epimutation (PHP1B).
|
25591844 |
2015 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Pediatric Cranial Vault Fractures: Analysis of Demographics, Injury Patterns, and Factors Predictive of Mortality.
|
26267576 |
2015 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Genomic study revealed no GNAS mutation.He had POH and PHP Ia.
|
25894639 |
2015 |
|
Pseudohypoparathyroidism, Type Ia
|
0.800 |
GeneticVariation
|
disease |
BEFREE |
Loss-of-function GNAS mutations lead to hormone resistance and Albright's hereditary osteodystrophy (AHO) when maternally inherited, i.e. pseudohypoparathyroidism-Ia (PHPIa), but cause AHO alone when located on the paternal allele, i.e. pseudoPHP (PPHP).
|
25464124 |
2015 |