scholarly journals Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing

2017 ◽  
Vol 61 (6) ◽  
pp. 633-636 ◽  
Author(s):  
Fernanda A. Correa ◽  
Marcela M. França ◽  
Qing Fang ◽  
Qianyi Ma ◽  
Tania A. Bachega ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Bone Age ◽  
Hormone Deficiency ◽  
Ghrh Receptor ◽  
Whole Exome

scholarly journals Whole Exome Sequencing Uncovered the Genetic Architecture of Growth Hormone Deficiency Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenxi Yu ◽  
Bobo Xie ◽  
Zhengye Zhao ◽  
Sen Zhao ◽  
Lian Liu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Molecular Diagnosis ◽  
Hormone Deficiency ◽  
Clinical Criteria ◽  
Mutational Burden ◽  
Group I ◽  
Whole Exome

PurposeCongenital growth hormone deficiency (GHD) is a rare and etiologically heterogeneous disease. We aim to screen disease-causing mutations of GHD in a relatively sizable cohort and discover underlying mechanisms via a candidate gene-based mutational burden analysis.MethodsWe retrospectively analyzed 109 short stature patients associated with hormone deficiency. All patients were classified into two groups: Group I (n=45) with definitive GHD and Group II (n=64) with possible GHD. We analyzed correlation consistency between clinical criteria and molecular findings by whole exome sequencing (WES) in two groups. The patients without a molecular diagnosis (n=90) were compared with 942 in-house controls for the mutational burden of rare mutations in 259 genes biologically related with the GH axis.ResultsIn 19 patients with molecular diagnosis, we found 5 possible GHD patients received known molecular diagnosis associated with GHD (NF1 [c.2329T>A, c.7131C>G], GHRHR [c.731G>A], STAT5B [c.1102delC], HRAS [c.187_207dup]). By mutational burden analysis of predicted deleterious variants in 90 patients without molecular diagnosis, we found that POLR3A (p = 0.005), SUFU (p = 0.006), LHX3 (p = 0.021) and CREB3L4 (p = 0.040) represented top genes enriched in GHD patients.ConclusionOur study revealed the discrepancies between the laboratory testing and molecular diagnosis of GHD. These differences should be considered when for an accurate diagnosis of GHD. We also identified four candidate genes that might be associated with GHD.

Transient impairment or delay of urinary trihydroxypregnanone (THS) response to metyrapone in boys with delayed adolescence and in patients with isolated growth hormone deficiency

1982 ◽  
Vol 99 (2) ◽  
pp. 166-173 ◽  
Author(s):  
M. Zachmann ◽  
D. Tassinari ◽  
W. Sorgo ◽  
G. U. Exner ◽  
B. Kempken ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Single Dose ◽  
Growth Hormone Deficiency ◽  
Bone Age ◽  
Urine Samples ◽  
Hormone Deficiency ◽  
Cortisol Response ◽  
Transient Impairment ◽  
Group A ◽  
Group B

Abstract. Twentythree boys with delayed adolescence (age 15.7 ± 2.0, bone age 12.4 ± 2.1 years) were studied. Their cortisol response to insulin was normal. After oral metyrapone (500 mg/m2 by mouth) one to three consecutive 12 h urine samples were collected for analysis of THS. Thirtyseven tests with 37 first, 21 second, and 11 third samples were carried out. The results could be divided into two main groups: 25 tests (group A) were subnormal in the first sample, 12 of them with a very weak (40 ± 8 μg/m2/12 h) and 13 with an insufficient (191 ± 16 μg/m2/12 h) THS response. Values in the second and third sample were higher, indicating a dealyed response. In 12 tests (group B), the results were normal (1016 ± 143 μg/m2/12 h) in the first and lower in the second and third samples. In three patients with repeated tests, there was improvement with increasing bone age. The THS-responses to metyrapone did not correlate with those of growth hormone, gonadotrophins, and TSH to stimuli. It is concluded that the THS-response to a single dose of metyrapone may be temporarily insufficient or delayed in delayed adolescence. We interpret this finding as showing transiently reduced or slow hypothalamic responsiveness.

scholarly journals Síndrome de Klinefelter con deficiencia parcial de hormona de crecimiento.

2015 ◽  
Vol 10 (1) ◽  
pp. 38
Author(s):  
Carlos TORI TORI ◽  
Carlos ROE B.
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Klinefelter Syndrome ◽  
Bone Age ◽  
Hormone Deficiency ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
The Third ◽  
Rare Association

We present a case of Klinefelter’s syndrome and short stature due to partial growth hormone deficiency. His height was below the third percentile for age and his bone age lagged behind four years. Cases like this are generally due to the presence of a an isochromosome Xq or to an isolated partial or total deficiency of growth hormone, or to partial or panhypopituitarism. We wish de emphasize the rare association between Klinefelter syndrome and growth hormone deficiency.

Current Dosing of Growth Hormone in Children With Growth Hormone Deficiency: How Physiologic?

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_3) ◽  
pp. 527-530
Author(s):  
Margaret H. MacGillivray ◽  
Sandra L. Blethen ◽  
John G. Buchlis ◽  
Richard R. Clopper ◽  
David E. Sandberg ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adverse Events ◽  
Growth Hormone Deficiency ◽  
Growth Velocity ◽  
Bone Age ◽  
Early Initiation ◽  
Hormone Deficiency ◽  
Treatment Result ◽  
Recombinant Growth Hormone ◽  
Pituitary Growth Hormone

The current doses of recombinant growth hormone (rGH) are two to three times those used in the pituitary growth hormone era. These rGH doses (0.025 to 0.043 mg/kg/d) are similar to or moderately greater than the physiologic requirements. Growth velocity and height gains have been shown to be greater with 0.05 mg/kg/d of rGH than with 0.025 mg/kg/d. Larger doses of GH and early initiation of treatment result in greater heights at the onset of puberty and greater adult heights. Earlier onset of puberty and more rapid maturation, as indicated by bone age, were not observed in children who were given 0.18 to 0.3 mg/kg/wk of rGH. The frequency of adverse events is very low, but diligent surveillance of all children who are treated with rGH is essential.

scholarly journals Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of MAGEL2-related disorders

2018 ◽  
Vol 55 (5) ◽  
pp. 316-321 ◽  
Author(s):  
Rebekah Jobling ◽  
Dimitri James Stavropoulos ◽  
Christian R Marshall ◽  
Cheryl Cytrynbaum ◽  
Michelle M Axford ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Clinical Manifestations ◽  
Rare Condition ◽  
Hormone Deficiency ◽  
Truncated Protein ◽  
Dysmorphic Features ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
And Inversion

BackgroundChitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified.Methods and resultsWe identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome. Through whole exome or whole genome sequencing, pathogenic variants in the MAGEL2 gene were identified in all affected patients. All disease-causing sequence variants detected are predicted to result in a truncated protein, including one complex variant that comprised a deletion and inversion.ConclusionsChitayat-Hall syndrome is caused by pathogenic variants in MAGEL2 and shares a common aetiology with the recently described Schaaf-Yang syndrome. The phenotype of MAGEL2-related disorders is expanded to include growth hormone deficiency as an important and treatable complication.

The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency

1989 ◽  
Vol 120 (6) ◽  
pp. 795-799 ◽  
Author(s):  
Jean Edmond Toublanc ◽  
Claire Couprie ◽  
Philippe Garnier ◽  
Jean-Claude Job
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Final Height ◽  
Bone Age ◽  
Hormone Deficiency ◽  
Gnrh Analogue ◽  
Isolated Growth Hormone Deficiency ◽  
One Year ◽  
Long Acting

Abstract. The final height of patients treated with growth hormone for isolated growth hormone deficiency has, up to now, been subnormal, with a mean below −2 sd in the series reported, an insufficient height at the onset of puberty and a more or less accelerated bone maturation during puberty being two important factors of the poor results. A long-acting analogue of gonadoliberin, Trp6-GnRH, has been given to GH-treated patients with isolated growth hormone deficiency at the time they reached pubertal stage 2, in combination with unchanged doses of GH, for one year in 11 and for two years in 7 of them. It resulted in an increase in the height age/bone age ratio and a reduction of the height insufficiency for bone age. The increase was slight but significant after one year, and fair after two years, in spite of a reduced annual growth rate. Post-analogue follow-up in 5 patients with continued GH treatment showed a good development of growth and of puberty. It is concluded that combination of the long-acting Trp6-GnRH analogue and GH for 1–2 years in patients with isolated growth hormone deficiency whose puberty starts with a very insufficient height may be an appropriate way to improve their growth parameters. Studies with increased doses of GH or increased frequency of injections could help to optimize the results. Several years of follow-up are needed for demonstrating the results on final height.

scholarly journals Adult height prediction by bone age determination in children with isolated growth hormone deficiency

2020 ◽  
Vol 9 (5) ◽  
pp. 370-378
Author(s):  
Thomas Reinehr ◽  
Martin Carlsson ◽  
Dionisios Chrysis ◽  
Cecilia Camacho-Hübner
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Adult Height ◽  
Age Determination ◽  
Bone Age ◽  
Hormone Deficiency ◽  
Gh Treatment ◽  
Height Prediction ◽  
The Mean ◽  
Tw2 Method

Background The precision of adult height prediction by bone age determination in children with idiopathic growth hormone deficiency (IGHD) is unknown. Methods The near adult height (NAH) of patients with IGHD in the KIGS database was compared retrospectively to adult height prediction calculated by the Bayley–Pinneau (BP) prediction based on bone age by Greulich–Pyle (GP) in 315 children and based on the Tanner-Whitehouse 2 (TW2) method in 121 children. Multiple linear regression analyses adjusted for age at GH start, age at puberty, mean dose and years of of GH treatment, and maximum GH peak in stimulation test were calculated. Results The mean underestimation of adult height based on the BP method was at baseline 4.1 ± 0.7 cm in girls and 6.1 ± 0.6 cm in boys, at 1 year of GH treatment 2.5 ± 0.5 cm in girls and 0.9 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 0.4 ± 0.6 cm in girls and 3.8 ± 0.5 cm in boys. The mean underestimation of adult height based on the TW2 method was at baseline 5.3 ± 2.0 cm in girls and 7.9 ± 0.8 cm in boys, at 1 year of GH treatment adult height was overestimated in girls 0.1 ± 0.6 cm in girls and underestimated 4.1 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 3.1 ± 1.5 cm in girls and 3.6 ± 0.8 cm in boys. Conclusions Height prediction by BP and TW2 at onset of GH treatment underestimates adult height in prepubertal IGHD children, while in mean 6 years after onset of GH treatment these prediction methods overestimated adult height.

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