Endoplasmic reticulum stress and apoptosis contribute to the pathogenesis of dominantly inherited isolated GH deficiency due to GH1 gene splice site mutations.
These growth curves constitute a model not only for primary, hereditary insulin-like growth factor-I (IGF-I) deficiency (Laron syndrome) but also for untreated secondary IGF-I deficiencies such as growth hormone gene deletion and idiopathic congenital isolated growth hormone deficiency.
This study aimed to assess attainment of genetic height potential after long-term growth hormone (GH) treatment in GH-naïve children diagnosed with isolated growth hormone deficiency (IGHD), multiple pituitary hormone deficiency (MPHD), born small for gestational age (SGA), or idiopathic short stature (ISS) enrolled in the American Norditropin®
In the present report we describe a novel 456G>A heterozygous mutation of splicing of the last base of the 3'-acceptor splice site of exon 4 within the GH1 in a 4.2-year old, extremely short (-5.32 height sDs) girl with congenital IGHD. the mutation involves a highly conserved GGGgtg sequence of the exon 4/IVs4 boundary region of the GH1 gene. the predicted effect of the 456 G>A mutation is perturbed splicing with possible skipping of exon 4 of the GH1 gene. the novel heterozygous 456 G>A mutation in exon 4 expands the spectrum of dominant negative splicing defects within the GH1 gene, responsible for congenital IGHD.
The distribution and frequency of the distinct haplotypes in the hGH gene family revealed no differences between IGHD (n = 30 chromosomes) and controls (n = 48 chromosomes).
We report on two sibs with familial isolated growth hormone deficiency (IGHD) resulting from homozygosity for a 7.6 kb deletion within the growth hormone gene cluster.
Thus, in at least four of the nine families, the mutation responsible for isolated growth hormone deficiency is not within or near the structural gene for growth hormone on chromosome 17.
G to A transition at position 6664 of the GH-1 gene results in the substitution of Arg183 by His (R183H) in human GH protein and causes a new form of autosomal dominant isolated GH deficiency (type II).
G to A transition at position 6664 of the growth hormone (GH-1) gene results in the substitution of Arg183 by His (R183H) in the GH protein and causes a new form of autosomal dominant isolated GH deficiency (IGHD type II).
Systematic profiling of clinical missence mutation effects on the intermolecular interaction between human growth hormone and its receptor in isolated growth hormone deficiency.
A model of isolated growth hormone deficiency may clarify if the lack of growth hormone is associated with increased susceptibility to infections, or with an altered responsiveness of the immune system.
Crossover sites resulting from unequal recombination within the human growth hormone (GH) gene cluster that cause GH1 gene deletions and isolated GH deficiency type 1A were localized in nine patients.
A heterozygous single base mutation in the human growth hormone (GH) gene (GH-1) was identified in a family presenting with isolated GH deficiency type II (IGHD II).
The GH1 gene mutation in the second family (IGHD I) was found, in a previous study, to be a G-->C transversion altering the first base of the donor splice site of intron IV.
In the multiple pituitary hormone deficiency (MPHD) group (n=50), first year GH response was significantly greater than in the isolated GH deficiency (IGHD) group (n=17) (p=0.030).
Isolated growth hormone deficiency type-2 (IGHD-2), the autosomal-dominant form of GH deficiency, is mainly caused by specific splicing mutations in the human growth hormone (hGH) gene (GH-1).
At least three different sizes of GH-1 gene deletions (approximately 6.7, 7.0 and 7.6 kilobases) have been detected by Southern blot analysis of DNA from individuals with familial isolated GH deficiency type IA (IGHD1A).
This study shows that GH-1 mutations are absent in 5/30 (16.6%) of the families with autosomal-dominant IGHD and raises the possibility that mutations in other gene(s) may be involved in IGHD with this mode of transmission.
Two siblings with isolated GH deficiency due to loss-of-function mutation in the GHRHR gene: successful treatment with growth hormone despite late admission and severe growth retardation.