scholarly journals Identification of a Novel Mutation in a Pseudohypoparathyroidism Family

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Zhi-Min Miao ◽  
Can Wang ◽  
Bin-Bin Wang ◽  
Dong-Mei Meng ◽  
Dong-Mei Su ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Clinical Manifestations ◽  
Thyroid Stimulating Hormone ◽  
Functional Study ◽  
Gnas Gene ◽  
Stimulatory G Protein ◽  
Type Ia ◽  
G Protein Alpha Subunit ◽  
Protein Alpha Subunit

Pseudohypoparathyroidism type Ia (PHP Ia) is defined as a series of disorders characterized by multihormone resistance in end-organs and Albright hereditary osteodystrophy (AHO) phenotype. PHP Ia is caused by heterozygous inactivating mutations in GNAS, which encodes the stimulatory G-protein alpha subunit (Gsa). A patient with typical clinical manifestations of pseudohypoparathyroidism (PHP) (round face, short stature, centripetal obesity, brachydactyly, and multi-hormone resistance: parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), and gonadotropins) presented at our center. The sequence of the GNAS gene from the patient and her families revealed a novel missense mutation (Y318H) in the proband and her mother. An in vitro Gsa functional study showed that Gsa function was significantly impaired. These results stress the importance of GNAS gene investigation.

Lack of GNAS re-methylation during oogenesis may be a cause of sporadic pseudohypoparathyroidism type Ib (PHP1B)

2021 ◽  
Author(s):  
Angelo Milioto ◽  
Monica Reyes ◽  
Patrick Hanna ◽  
Zentaro Kiuchi ◽  
Serap Turan ◽  
...  
Keyword(s):  
Underlying Disease ◽  
Renal Tubules ◽  
Vitro Fertilization ◽  
Stimulatory G Protein ◽  
G Protein Alpha Subunit ◽  
Methylation Defects ◽  
Pth Resistance ◽  
Protein Alpha Subunit ◽  
Male Factors

Abstract Context Pseudohypoparathyroidism type Ib (PHP1B) is characterized by hypocalcemia and hyperphosphatemia due to PTH-resistance in the proximal renal tubules. Maternal pathogenic STX16/GNAS variants leading to maternal epigenetic GNAS changes impair expression of the stimulatory G protein alpha-subunit (Gsα) thereby causing autosomal dominant PHP1B (AD-PHP1B). In contrast, genetic defects responsible for sporadic PHP1B (sporPHP1B) remain mostly unknown. Objective Determine whether PHP1B encountered after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) causes GNAS re-methylation defects similar to those in sporPHP1B. Design Retrospective analysis. Results Nine among thirty-six sporPHP1B patients investigated since 2000, all with LOM at the three maternal GNAS DMRs and gain-of-methylation (GOM) at the paternal NESP DMR, had been conceived through IVF or ICSI. Besides abnormal GNAS methylation, IVF/ICSI-PHP1B cases revealed no additional imprinting defects. Three of these PHP1B patients have dizygotic twins and four have IVF/ICSI-conceived siblings, all with normal GNAS methylation; two unaffected younger siblings were conceived naturally. Conclusion Sporadic and IVF/ICSI-conceived PHP1B patients revealed indistinguishable epigenetic changes at all four GNAS DMRs thus suggesting a similar underlying disease mechanism. Given that re-methylation at the three maternal DMRs occurs during oogenesis, male factors are unlikely to cause LOM post-fertilization. Instead, at least some of the sporPHP1B variants could be caused by a defect(s) in an oocyte-expressed gene that is required for fertility and for re-establishing maternal GNAS methylation imprints. It remains uncertain, however, whether lack of GNAS re-methylation alone impairs oocyte maturation because of insufficient Gsα expression, thus necessitating Assisted Reproductive Technology (ART) for conception.

scholarly journals A novel mutation in a newborn baby leading to glycogen storage disease type Ia

2018 ◽  
Vol 21 (2) ◽  
pp. 55-57
Author(s):  
S Dorum ◽  
O Gorukmez
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Clinical Manifestations ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Clinical Findings ◽  
Disease Type ◽  
Type Ia

Abstract Glycogen storage disease type Ia (GSD1A) is caused by mutations in the G6PC gene. The G6PC gene was first cloned in 1993. Since then, many different mutations have been identified leading to this disease. Hepatomegaly is one of the important clinical manifestations of the disease. A 23-day-old girl was admitted to the hospital due to respiratory distress. Her physical examination was normal except for tachypnea. She had hypoglycemia, lactic academia, hyperlipidemia and hyperuricemia. With these clinical findings, GSD1A was considered in the patient and the diagnosis was genetically confirmed. By direct sequencing of the G6PC gene, we identified a novel homozygous variation (c.137T>G/p.Leu46Arg) in the patient and the healthy mother and father were heterozygotes for the variant. Here we present a case with a novel homozygous missense mutation c.137T>G/p.Leu46Arg in the G6PC gene leading to GSD1A clinical findings except early hepatomegaly. These findings expand the spectrum of causative mutations, and clinical findings in GSD1A.

scholarly journals Isolation and expression of a novel chick G-protein cDNA coding for a Gαi3 protein with a Gα0 N-terminus

1994 ◽  
Vol 297 (2) ◽  
pp. 303-308 ◽  
Author(s):  
E J Kilbourne ◽  
J B Galper
Keyword(s):  
G Protein ◽  
Sequence Similarity ◽  
In Vitro Transcription ◽  
Alpha Subunit ◽  
Alpha Subunits ◽  
N Terminus ◽  
Brain Cdna Library ◽  
G Protein Alpha Subunit ◽  
Protein Alpha Subunit

We have cloned cDNAs coding for G-protein alpha subunits from a chick brain cDNA library. Based on sequence similarity to G-protein alpha subunits from other eukaryotes, one clone was designated G alpha i3. A second clone, G alpha i3-o, was identical to the G alpha i3 clone over 932 bases on the 3′ end. The 5′ end of G alpha i3-o, however, contained an alternative sequence in which the first 45 amino acids coded for are 100% identical to the conserved N-terminus of G alpha o from species such as rat, mouse, human, bovine and hamster. Both clones were found to be expressed in all tissues studied. The unusual alpha o-alpha i3-like G-protein chimera, G alpha i3-o, was found to be expressed at significantly lower levels than G alpha i3. In vitro transcription and translation of the G alpha i3-o cDNA clone gave a protein of approx. 41 kDa which stably bound guanosine 5′-[gamma-thio]triphosphate. G alpha i3-o appears to be the first G-protein alpha subunit cloned which contains ends that are homologous to two different alpha subunit isoforms, G alpha o and G alpha i3.

scholarly journals A novel GNAS mutation in pseudohypoparathyroidism type 1a in a Chinese man presented with recurrent seizure: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Difei Lu ◽  
Aimei Dong ◽  
Junqing Zhang ◽  
Xiaohui Guo
Keyword(s):  
Thyroid Stimulating Hormone ◽  
Guanine Nucleotide Binding Protein ◽  
Recurrent Seizure ◽  
Case Presentation ◽  
Albright’S Hereditary Osteodystrophy ◽  
Gnas Gene ◽  
Albright's Hereditary Osteodystrophy ◽  
Guanine Nucleotide Binding ◽  
Protein Alpha Subunit ◽  
Gnas Mutation

Abstract Background Pseudohypoparathyroidism is a rare genetic disease characterized by hypocalcaemia and hyperphosphataemia due to the defect to the guanine nucleotide-binding protein alpha subunit (GNAS) gene. Patients with pseudoparathyroidism type 1a and 1c could manifest Albright’s hereditary osteodystrophy and multiple hormone resistance including gonadotropin and thyroid stimulating hormone. Case presentation Here we report a Chinese man who presented with fatigue, recurrent seizure and Albright’s hereditary osteodystrophy. His genetic study revealed a heterozygote mutation in the GNAS gene [NM_000516.4(GNAS): c2787_2788del (p.Val930AspfsTer12)]. After calcium and calcitriol supplement, his seizures achieved partially remission. Conclusions We report a case of PHP1a or 1c with a novel frameshift mutation in GNAS gene in a patient presenting with AHO, as well as TSH and partial gonadotropin resistance. This mutation in this case has not been reported in literature and adds to the spectrum of genetic mutations related to PHP.

Sign in / Sign up

Export Citation Format

Share Document