scholarly journals A novel inactivating mutation of the LH/chorionic gonadotrophin receptor with impaired membrane trafficking leading to Leydig cell hypoplasia type 1

2015 ◽  
Vol 172 (6) ◽  
pp. K27-K36 ◽  
Author(s):  
Adolfo Rivero-Müller ◽  
Iulia Potorac ◽  
Axelle Pintiaux ◽  
Adrian F Daly ◽  
Albert Thiry ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Membrane Trafficking ◽  
Novel Mutation ◽  
Chorionic Gonadotrophin ◽  
Molecular Characteristics ◽  
Structural Domain ◽  
Cell Trafficking ◽  
The Impact ◽  
Leydig Cell Hypoplasia

ObjectiveThe LH/chorionic gonadotrophin receptor (LHCGR) is a G protein-coupled receptor (GPCR) that plays a central role in male sexual differentiation, regulation of ovarian follicular maturation, ovulation and maintenance of corpus luteum and pregnancy, as well as maintenance of testicular testosterone production. Mutations in theLHCGRgene are very rare. The aim of this work was to study the clinical and molecular characteristics of a rare familialLHCGRmutation.MethodsFive affected members of a family, including a phenotypically female, but genotypically male (46,XY), patient with Leydig cell hypoplasia type 1 and four genotypically female siblings with reproductive abnormalities, were studied genetically. Cell trafficking studies as well as signalling studies of mutated receptor were performed.ResultsThe five affected patients were all homozygous for a novel mutation in theLHCGRgene, a deletion of guanine in position 1850 (1850delG). This resulted in a frameshift affecting most of the C-terminal intracellular domain.In vitrostudies demonstrated that the 1850delG receptor was completely incapable of transit to the cell membrane, becoming trapped within the endoplasmic reticulum. This could not be rescued by small-molecule agonist treatment or stimulated intracellularly by co-expression of a yoked human chorionic gonadotrophin.ConclusionsThis novelLHCGRmutation leads to complete inactivation of the LHCGR receptor due to trafficking and signalling abnormalities, which improves our understanding of the impact of the affected structural domain on receptor trafficking and function.

Novel compound heterozygous variants in the LHCGR gene identified in a subject with Leydig cell hypoplasia type 1

2018 ◽  
Vol 31 (2) ◽  
pp. 239-245 ◽  
Author(s):  
Yufei Xu ◽  
Yulin Chen ◽  
Niu Li ◽  
Xuyun Hu ◽  
Guoqiang Li ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Splice Site Mutation ◽  
Molecular Characteristics ◽  
Compound Heterozygous ◽  
Site Mutation ◽  
Family Pedigree ◽  
Correlation Spectrum ◽  
Compound Heterozygous Variants ◽  
Leydig Cell Hypoplasia

Abstract Background: Leydig cell hypoplasia (LCH) is a rare disease and one of the causes of male disorder of sexual differentiation (DSD). Inactivating mutations in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene account for the underlying LCH pathogenicity. This study aimed to analyze the clinical presentation and diagnosis as well as highlight the molecular characteristics of a subject with LCH type 1. Case presentation: Clinical data were collected from the subject and analyzed. Next generation sequencing of the immediate family pedigree using peripheral blood genomic DNA was performed, and the relevant mutations were verified with Sanger sequencing. We describe the case of a 5-year-old patient with DSD, presenting with a lateral inguinal hernia accompanied by abnormal hormone tests. The genetic analysis revealed novel compound heterozygous variants in the LHCGR gene, including a splice site mutation (c.681-1 G>A) and a frameshift variant (c.1582_1585del ATAT, p.Ile528*). Conclusions: We identified novel compound heterozygous variants in the LHCGR gene, and expanded the genotype-phenotype correlation spectrum of LHCGR variants.

A novel variant in LCHGR gene in 3 siblings with type 1 Leydig cell hypoplasia

2020 ◽  
Vol 36 (12) ◽  
pp. 1136-1139
Author(s):  
Amine Aktar Karakaya ◽  
Edip Unal ◽  
Aslı Beştaş ◽  
Funda Taş ◽  
Hüseyin Onay ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Novel Variant ◽  
Leydig Cell Hypoplasia

scholarly journals Biological Effect of a Novel Mutation in the Third Leucine-Rich Repeat of Human Luteinizing Hormone Receptor

2006 ◽  
Vol 20 (10) ◽  
pp. 2493-2503 ◽  
Author(s):  
Michael Yiu-Kwong Leung ◽  
Peter J. Steinbach ◽  
Deborah Bear ◽  
Vanessa Baxendale ◽  
Patricia Y. Fechner ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Ligand Binding ◽  
Leydig Cell ◽  
Novel Mutation ◽  
Luteinizing Hormone Receptor ◽  
Nucleotide Sequencing ◽  
Heterozygous Mutation ◽  
Leucine Rich Repeat ◽  
The Third ◽  
Leydig Cell Hypoplasia

Abstract A novel heterozygous mutation A340T leading to the substitution of Phe for the conserved amino acid Ile114 was identified by nucleotide sequencing of the human LH/chorionic gonadotropin receptor (hLHR) of a patient with Leydig cell hypoplasia. This mutation is located in the third leucine-rich repeat in the ectodomain of the hLHR. In vitro expression studies demonstrated that this mutation results in reduced ligand binding and signal transduction of the receptor. Studies of hLHR constructs in which various amino acids were substituted for the conserved Ile114 showed that receptor activity is sensitive to changes in size, shape, and charge of the side chain. A homology model of the wild-type hLHR ectodomain was made, illustrating the packing of conserved hydrophobic side chains in the protein core. Substitution of Ile114 by Phe might disrupt intermolecular contacts between hormone and receptor. This mutation might also affect an LHR-dimer interaction. Thus, the I114F mutation reduces ligand binding and signal transduction by the hLHR, and it is partially responsible for Leydig cell hypoplasia in the patient.

scholarly journals Leydig cell hypoplasia type 1 diagnosed in early childhood with inactivating mutation in LHCGR gene

2021 ◽  
Vol 2021 (4) ◽  
Author(s):  
Fatma Özgüç Çömlek ◽  
Raif Yıldız ◽  
Fatma Seyrek ◽  
Filiz Tütüncüler
Keyword(s):  
Early Childhood ◽  
Leydig Cell ◽  
Sexual Development ◽  
Autosomal Recessive ◽  
Pubertal Delay ◽  
Complete Form ◽  
Autosomal Recessive Condition ◽  
Inactivating Mutation ◽  
Leydig Cell Hypoplasia

ABSTRACT Leydig cell aplasia/hypoplasia is an autosomal recessive condition. In its complete form, these patients are 46XY but are cryptorchid and phenotypically female. Most cases reported in literature presented with in adolescence with pubertal delay. We reported a case with a predefined mutation in the LHCGR gene, presenting with swelling in the inguinal region and therefore diagnosed in early childhood. We wanted to emphasize the necessity of keeping Leydig cell hypoplasia in mind in the differential diagnosis of sexual development disorders in early childhood.

The impact of real-time continuous glucose monitoring on metabolic control in children with type 1 diabetes

2020 ◽  
Author(s):  
Ruxandra Calapod Ioana ◽  
Irina Bojoga ◽  
Duta Simona Gabriela ◽  
Ana-Maria Stancu ◽  
Amalia Arhire ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Real Time ◽  
Metabolic Control ◽  
Continuous Glucose Monitoring ◽  
Glucose Monitoring ◽  
The Impact

Model estimates of the results of diabetes patients using modern glucometers with tri-color technology for displaying test results

2019 ◽  
pp. 81-89
Author(s):  
Larisa Dmitrievna Popovich ◽  
Svetlana Valentinovna Svetlichnaya ◽  
Aleksandr Alekseevich Moiseev
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Economic Benefits ◽  
Test Results ◽  
Self Monitoring ◽  
Patients With Diabetes ◽  
The Impact

Diabetes – a disease in which the effect of the treatment substantially depends on the patient. Known a study showed that the use of glucometers with the technology of three-color display of test results facilitates self-monitoring of blood sugar and leads to a decrease in glycated hemoglobin (HbAlc). Purpose of the study: to modeling the impact of using of a glucometer with a color-coded display on the clinical outcomes of diabetes mellitus and calculating, the potential economic benefits of reducing the hospitalization rate of patients with diabetes. Material and methods. Based on data from two studies (O. Schnell et al. and M. Baxter et al.) simulation of the reduction in the number of complications with the use of a glucometer with a color indication. In a study by O. Schnell et al. a decrease of HbA1c by 0.69 percent is shown when using the considered type of glucometers, which was the basis of the model. Results. In the model, the use of a glucometer with a color-coded display for type 1 diabetes led to a decrease in the total number of complications by 9.2 thousand over 5 years per a cohort of 40 thousand patients with different initial levels of HbA1c. In a cohort of 40 thousand patients with type 2 diabetes, the simulated number of prevented complications was 1.7 thousand over 5 years. When extrapolating these data to all patients with diabetes included in the federal register of diabetes mellitus (FRD), the number of prevented complications was 55.4 thousand cases for type 1 diabetes and 67.1 thousand cases for type 2 diabetes. The possible economic effect from the use of the device by all patients with a diagnosis of diabetes, which are included in the FRD, estimated at 1.5 billion rubles for a cohort of patients with type 1 diabetes and 5.3 billion rubles for patients with type 2 diabetes. Conclusion. Improving the effectiveness of self-monitoring, which is the result of the use of glucometers with color indicators, can potentially significantly reduce the incidence of complications in diabetes and thereby provide significant economic benefits to society.

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