Characterization of a de Novo 43-bp Deletion of the Gsα Gene (GNAS1) in Albright Hereditary Osteodystrophy

Luttikhuis, Monique E.M.Oude; Wilson, Louise C.; Leonard, James V.; Trembath, Richard C.

doi:10.1006/geno.1994.1297

Cited by 46 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The R231H mutation was reported previously . Data for mutations were derived from the following references (Ahmed et al 1998;Farfel et al 1996;Fischer et al 1998;Iiri et al 1994;Miric et al 1993;Oude-Luttikhuis et al 1994;Pattern et al 1990;Schwindinger et al 1994;Shapira et al 1996;Warner et al 1997Warner et al , 1998Weinstein et al 1990Weinstein et al , 1992Yu et al 1995Yu et al , 1999 NA, Not available; PTH, parathyroid hormone; TRH, thyroidstimulating hormone (TSH) releasing hormone; T4, thyroxine; T3, triiodothyronine a PTH infusion test was performed using bolus synthetic PTH-(1-34), at 100 U/m 2 . Basal levels are the mean urinary cyclic (c)AMP (nmol/h) and urinary phosphate-to-creatine ratio for two urine samples taken in the 2 h before the administration of PTH.…”

Section: Patientmentioning

confidence: 99%

Two mutations of the Gsα gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia

et al. 2001

View full text Add to dashboard Cite

Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the α-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsα gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the γ subunit of Gsα protein, this mutation may impair Gs protein function. We report here one novel Gsα mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous.

show abstract

Section: Patientmentioning

confidence: 99%

Two mutations of the Gsα gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Taken together, the clinical, molecular and family history data confirm somatic mosaicism. While de novo mutations in GNAS1 have been reported in PHP1a and PPHP patients previously [Luttikhuis et al, 1994;Yu et al, 1995], somatic mosaicism for a GNAS mutation has been not been reported previously in the literature. Aldred et al published one family in which germline mosaicism for a GNAS mutation was ascertained through comparing the maternal haplotype of siblings affected and unaffected with PHP1a.…”

Section: Discussionmentioning

confidence: 79%

Pseudohypoparathyroidism type 1a and the GNAS p.R231H mutation: Somatic mosaicism in a mother with two affected sons

Ngai

Chijiwa

Mercimek-Mahmutoglu

et al. 2010

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Pseudohypoparathyrodism (PHP) is a disorder caused by mutations in the guanine nucleotide-binding α-subunit (GNAS). We sought to determine the genetic origin of PHP1a in one affected family. We identified the previously reported Gsα R231H mutation in family members affected with PHP1a. DNA analysis found that the two clinically affected sons are heterozygous for the mutation. The sons have PHP1a, manifesting obesity, intellectual disability, hypogonadism, hypothyroidism and elevated PTH levels. Initial DNA sequencing did not detect the mutation in either parent. However, their mother displayed some features of PHP, including elevated PTH levels and asymmetrical metacarpal shortening. Using molecular cloning, we detected the mutation at low levels in the mother's leukocyte DNA, consistent with somatic mosaicism and her mildly affected status. Thus, we have identified additional cases of PHP1a caused by the Gsα R231H mutation. In this family, the mother has a milder phenotype due in part to somatic mosaicism, whereas the two affected sons have full PHP1a. Though somatic mosaicism for activating GNAS mutations is known to occur in McCune-Albright syndrome, this is the first report confirming somatic mosaicism for a hypofunctioning GNAS mutation in a PHP kindred.

show abstract

“…Exons 2, 4, 5 and 7-13 of the GSa gene were amplified by the polymerase chain reaction (PCR) and specific primer pairs as described before [12,19] [11][12][13][14][15][16][17][18][19][20]27], but no mutation of the Ca gene was found in "only AHO" family [28]. These are distributed throughout the gene with all but one located in exons 2-13.…”

Section: Resultsmentioning

confidence: 99%

“…Mutations of the GSa gene lead to either constitutive activation or loss of function in human diseases [10][11][12][13][14][15][16][17][18][19][20][21][22]. Molecular genetic studies have shown that PHP with AHO can result from heterozygous loss-of-function mutations in the gene encoding the GTP-binding protein GSa.…”

mentioning

confidence: 99%

Mutations in Exon 7 of the GTP-Binding Protein Gs.ALPHA. Were Not a Common Cause of Pseudohypoparathyroidism with Albright's Hereditary Osteodystrophy in Japanese.

et al. 1997

View full text Add to dashboard Cite

Abstract. The identification of unique point mutations in patients with pseudohypoparathyroidism (PHP) with Albright's hereditary osteodystrophy (AHO) in different ethinic backgrounds has proved that defects within the GSa gene account for GSa deficiency in those patients. To search a mutation hot spot of the GSa gene in Japanese patients, we have screened exons 2-13 of the GSa gene for mutations in three unrelated Japanese PHP patients with AHO. We could find no abnormalities by denaturing gradient gel electrophoresis and no mutations of sequencing of exon 7 in these subjects. This suggests that mutations in exon 7 of the GSa gene may not be a common cause of PHP with AHO in Japanese.

show abstract

Characterization of a de Novo 43-bp Deletion of the Gsα Gene (GNAS1) in Albright Hereditary Osteodystrophy

Cited by 46 publications

References 0 publications

Two mutations of the Gsα gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia

Two mutations of the Gsα gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia

Pseudohypoparathyroidism type 1a and the GNAS p.R231H mutation: Somatic mosaicism in a mother with two affected sons

Mutations in Exon 7 of the GTP-Binding Protein Gs.ALPHA. Were Not a Common Cause of Pseudohypoparathyroidism with Albright's Hereditary Osteodystrophy in Japanese.

Contact Info

Product

Resources

About