Mutations in IGSF10 cause self-limited delayed puberty, via disturbance of GnRH neuronal migration

2015 ◽  
Author(s):  
Sasha Howard ◽  
Leo Guasti ◽  
Gerard Ruiz-Babot ◽  
Alessandra Mancini ◽  
Alessia David ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Delayed Puberty

scholarly journals IGSF 10 mutations dysregulate gonadotropin‐releasing hormone neuronal migration resulting in delayed puberty

2016 ◽  
Vol 8 (6) ◽  
pp. 626-642 ◽  
Author(s):  
Sasha R Howard ◽  
Leonardo Guasti ◽  
Gerard Ruiz‐Babot ◽  
Alessandra Mancini ◽  
Alessia David ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Gonadotropin Releasing Hormone ◽  
Delayed Puberty ◽  
Releasing Hormone

scholarly journals Defects in the GnRH Neuronal Migration factor, CCDC141, Lead to Self-Limited Delayed Puberty

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A665-A666
Author(s):  
Tansit Saengkaew ◽  
Alessandra Mancini ◽  
Gerard Ruiz-Babot ◽  
Claudia P Cabrera ◽  
Michael R Barnes ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neuronal Migration ◽  
Hypogonadotropic Hypogonadism ◽  
Hek293 Cells ◽  
Delayed Puberty ◽  
Compound Heterozygous ◽  
Critical Element ◽  
Incomplete Penetrance ◽  
Inheritance Pattern ◽  
Foetal Development

Abstract GnRH neuronal biology has been identified as a critical element in the pathogenesis of self-limited DP, previously implicated exclusively in the pathophysiology of idiopathic hypogonadotropic hypogonadism (IHH). We hypothesise that this condition may be inherited via genetic variants discoverable through whole-exome sequencing (WES), by focusing on genes involved in GnRH neuron development and function, and genes reported in IHH. We analysed WES data from large Finnish cohort with familial self-limited DP, focusing on genes recently reported in IHH. WES data of 100 DP families have been analysed with a total of 193 individuals: 100 probands, 158 affected and 35 unaffected family members. Potentially pathogenic rare variants segregating within cohort families were identified using a virtual panel of recently reported IHH genes (n=13). This analysis identified 6 rare potentially pathogenic variants in CCDC141 in 25 individuals of 8 families which account for almost 10% of self-limited DP cases in this cohort, without variants identified in cohort control cases. Previous studies reported that homozygous or compound heterozygous mutations of CCDC141 cause Kallmann syndrome and IHH, due to impaired GnRH neuronal migration. In this study, all 6 CCDC141 variants were heterozygous missense variants predicted to be deleterious by in silico prediction tools. Most probands were male (n=7) with typical features of self-limited DP, with absence of secondary sexual characteristics, delayed bone age, and low gonadotropins and sex steroids at first presentation and spontaneous entry into puberty later than age of 14 years without treatment. The majority of pedigrees displayed good segregation of variants with the DP trait, following an autosomal dominant inheritance pattern. However, in two families, there was a complex inheritance pattern with compound heterozygosity (p.Ser55Cys and p.Asp767Asn) and possible incomplete penetrance. In vitro study showed that the overexpression of four key CCDC141 variants in HEK293 cells delayed cell migration, 72% in p.Ser55Cys (p=0.04), 66% in p.Gln507His (p=0.04), 65% in p.Asp767Asn (p=0.02), and 83% in p.Ala1073Thr (p=0.01), when compared to WT (100%). Moreover, WT-overexpressed cells increased the rate of cell migration when compared to non-transfected cells (100% vs 65%, p=0.005), reaffirming that CCDC141 has a role in cell migration. In conclusion, heterozygous deficiency of CCDC141, previously reported to cause IHH, can cause self-limited DP due to abnormal GnRH migration during foetal development.

THE HCG-TEST IN BOYS WITH DELAYED PUBERTY AND WITH TESTICULAR DAMAGE

1965 ◽  
Vol 49 (4_Suppl) ◽  
pp. S11
Author(s):  
C. G. Bergstrand
Keyword(s):  
Delayed Puberty ◽  
Testicular Damage ◽  
Hcg Test

TRH stimulates LH release in adolescents with delayed puberty

1986 ◽  
Vol 113 (1_Suppl) ◽  
pp. S33-S34
Author(s):  
W.D. HETZEL ◽  
U. SIEBLING ◽  
L. ABERLE
Keyword(s):  
Delayed Puberty ◽  
Lh Release

Mutations in HS6ST1 are causal in self-limited delayed puberty as well as idiopathic hypogonadotropic hypogonadism

2015 ◽  
Author(s):  
Sasha Howard ◽  
Ariel Poliandri ◽  
Helen Storr ◽  
Louise Metherell ◽  
Claudia Cabrera ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Delayed Puberty ◽  
Idiopathic Hypogonadotropic Hypogonadism

Delayed puberty vs hipogonadotropic hypogonadism; how long to wait to treat?

2018 ◽  
Author(s):  
Araceli Munoz-Garach ◽  
Cristina Diaz-Perdigones ◽  
Isabel Cornejo-Pareja ◽  
Isabel Mancha-Doblas ◽  
Francisco J Tinahones
Keyword(s):  
Delayed Puberty

State of the enzyme link of antioxidant protection in boys with hypoandrogenism

2020 ◽  
Vol 40 (4) ◽  
pp. 32-36
Author(s):  
L. K. Parkhomenko ◽  
◽  
L. A. Strashok ◽  
S. I. Turchina ◽  
G. V. Kosovtsova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Glutathione Peroxidase ◽  
Free Radical Oxidation ◽  
Conjugated Dienes ◽  
Delayed Puberty ◽  
Control Group ◽  
Antioxidant Protection ◽  
Radical Oxidation

Recently, interest in the problem of free radical oxidation in biological membranes, which is directly related to both the normal functioning of cells and the occurrence, course and outcome of many pathological conditions, has increased again in clinical medicine. The aim was to determine the role and impact of antioxidant defense in boys with hypoandrogenism. The study involved 75 adolescents with hypoandrogenism aged 13–18 years, who underwent a complex of clinical and laboratory examinations. All patients were conducted complex of anthropometric research and determination of the degree of delayed puberty, laboratory and instrumental examination. Free radical oxidation was determined by the levels of malondialdehyde, conjugated dienes, carbonated proteins, superoxide dismutase and catalase in the serum, and restored glutathione and glutathione peroxidase in whole blood. Based on their determination, the coefficient of oxidative stress was calculated. Statistical processing of results was performed using parametric and nonparametric methods. The study of indicators of the free radical oxidation process found that adolescents with hypoandrogenism have multidirectional changes in the oxidation of proteins and lipids, namely: the level of conjugated dienes increases, the concentration of malondialdehyde remains at the level of the control group, and the level of carbonated proteins tends to decrease. As for the activity of antioxidant protection enzymes, a significant decrease in the level of glutathione peroxidase was detected, while the level of superoxide dismutase and catalase remained at the level of normative indicators. Oxidative stress accompanies and is one of the pathogenetic links in the formation or maintenance of the state of hypoandrogenism in boys. This requires the use of antioxidants, the complex of which must be selected individually.

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