GH Gene Research Articles

Association Analysis between Exon II of GH Gene and Growth Traits in Sheep

Association Analysis between Exon II of GH Gene and Growth Traits in Sheep

Studying the effect of the genotypes of the GH gene on blood parameters and some structural characteristics of Iraqi buffalo milk

Studying the effect of the genotypes of the GH gene on blood parameters and some structural characteristics of Iraqi buffalo milk

GROWTH AND EXPRESSION PATTERN OF GROWTH-RELATED GENES IN THE FAST-GROWING GIANT GOURAMI Osphronemus goramy

Growth improvement of the giant gourami through molecular assisted selection offers a breakthrough solution regarding the slow growth problem in culturing the fish species. However, gene molecular expression studies and gene mapping information are scarce for this species. This study aimed to evaluate the growth, expression of the growth-related genes and compare the gene expressions between fast-growing (FG) and slow-growing (SG) fish. The polymorphism screenings were also conducted within the GH sequence of the FG and SG populations. Fish growth was analyzed by measuring length and weight once a month. The expression levels of GH, IGF1, AMPK, ARS-I, ALT, and AST genes were analyzed using real-time PCR. Twenty-five days old fish were reared for 30 days. The fish were continuously reared separately based on their body weight (BW) for 85 days until reaching 140 days old. At the end of the rearing period, the BW growth rate of the FG population was 1.569-fold higher, and body length (BL) growth was 1.056-fold higher than the SG population. FG fish have higher gene expression than the SG fish, indicating the important role of gene expression in fish growth. The polymorphisms screening within the GH sequences showed no significant difference between FG and SG fish of giant gourami. These research results provide valuable information in developing the marker-assisted selection for growth traits in giant gourami.

Evaluation of an Innovative and Sustainable Pre-Commercial Compound as Replacement of Fish Meal in Diets for Rainbow Trout during Pre-Fattening Phase: Effects on Growth Performances, Haematological Parameters and Fillet Quality Traits.

Simple SummaryThe study aims to define the potential and sustainable use of pre-commercial product ITTINSECT™ APS V1 as fish meal replacement in the diets of rainbow trout Oncorhynchus mykiss. For this, a 60 days feeding trail was performed by using diets with different replacing rate of fishmeal (0 (ITTM0), 25 (ITT25), 50 (ITT50), 75 (ITT75) and 100 (ITT100) %) with ITTINSECT™ APS V1. At the end of the feeding trial, significantly higher growth performance was observed in the group fed with the diet with a 25% and 50% substitution of fish meal by ITTINSECT™ APS V1. Moreover, the growth-related gene expressions analyzed in muscle tissue had significantly higher gene expression levels for these two diets (25% and 50% substitution) when compared to the control. The hematology values were found to be identical, whereas other parameters (such as serum total protein, globulins and glucose levels, or some immune-related gene expression) had different results among the experimental groups. In conclusion, replacement of fish meal with up to 50% ITTINSECT™ APS V1 in diets for rainbow trout is suggested in order to achieve the best growth performance in rainbow trout and enhance sustainable aquaculture practices.The aim of the study was to determine the potential and sustainable use of pre-commercial product ITTINSECT™ APS V1 as a major protein source in rainbow trout (Oncorhynchus mykiss) diets. A 60-day feeding experiment was conducted to potentially use ITTINSECT as fish meal replacement in the diets of rainbow trout. Five isonitrogenous in dry matter (38% crude protein) and isolipidic (15% crude lipid) diets were produced: a control diet (fishmeal-based) (ITT0) and four experimental diets replacing fishmeal by 25 (ITT25), 50 (ITT50), 75 (ITT75) and 100 (ITT100) %, with ITTINSECT™ APS V1. Triplicate tanks, containing 15 fish each (65.81 ± 1.26 g), were hand-fed to apparent satiation twice every day during the experiment. At the end of the feeding trial, significantly higher growth performance was observed in the group fed ITTM25 and ITTM50 diets. This performance was supported by growth-related gene expressions analyzed in muscle; significantly higher GH and IGF-I genes expression levels were determined in ITT25 and ITT50 when compared to control (ITT0) (p < 0.05). While no significant differences were found between the hematology values (p > 0.05), serum total protein, globulins and glucose levels were significantly different between experimental groups (p < 0.05). In addition to this, the immune-related genes such as TNF-α, IL8 and IL1-β expression levels were determined to be significantly different (p < 0.05). In conclusion, in order to achieve the best growth performance in rainbow trout and enhance sustainable aquaculture practices, replacement of fish meal with up to 50% ITTINSECT™ APS V1 in diets for rainbow trout is suggested.

GENETIC DIVERSITY OF THE CHICKEN LINES OF BELARUSIAN BREEDING BY ALLELIC COMPOSITION OF PRL, GH AND IGF-I GENES ASSOCIATED WITH PRODUCTIVITY

The genetic structure of the populations of the Rhode-Island Red chicken line K1 and the White Leghorn chicken line B(5) of the Belarusian selection was determined according to the 24 InDel and C-2402T polymorphisms of the prolactin gene PRL, MspI polymorphism in 1 and 4 introns of the growth hormone gene GH, as well as HinfI polymorphism of the insulin-like growth factor I gene IGF-I. It was shown that males and females of the White Leghorn chicken line B(5) of egg productivity and the Rhode-Island Red chicken line K1 of egg-meat productivity differ in the allele occurrence frequency of the studied genes. The alleles of the PRL and GH genes associated with increased egg productivity were the most widespread among the representatives of the White Leghorn chicken line B(5). The data obtained can be used&#x0D; for the targeted selection of the hens of the studied lines.

Fertility, Growth Rate, Polymorphism of GH and FUT1 Genes of Hybrid between Wild Boars and Indigenous Breeds

Fertility, Growth Rate, Polymorphism of GH and FUT1 Genes of Hybrid between Wild Boars and Indigenous Breeds

Preparation of GH/tPA double transgenic mice and gene expression analysis

To obtain GH/tPA double transgenic mice, analyze the expression level of tissue plasminogen activator (tPA) in the mammary glands and observe the growth and development of the transgenic mice. We obtained the offspring mice of 2 tPA single transgenic mice (P03 and P05) mated with a female nontransgenic mouse by microinjection of linearized GH plasmid into the fertilized eggs and embryo transfer. PCR was used to detect the gene integration. The expression levels of tPA in single gene and double gene transgenic mice were compared using ELISA and Western blotting. We assessed the effects of GH gene transduction on the growth and development of the transgenic mice by observing body weight changes of the mice at each developmental stage. A total of 286 fertilized eggs were collected from P03 mice, and after embryo transfer, 77 offspring mice were obtained, including 16 tPA single transgenic mice (7 male, 9 female) and 13 GH/tPA double transgenic mice (8 male, 5 female) as confirmed by PCR. The integration rate of the double genes was 16.9%. A total of 175 fertilized eggs were collected from P05 mice, and 34 offspring mice were obtained including 12 tPA single transgenic mice (5 male, 7 female) and 7 GH/tPA double transgenic mice (3 male, 4 female), in which the integration rate of the double genes was 20.6%. The highest expression level of tPA in the mammary gland was significantly higher in double than in single transgenic mice (674 μg/mL vs 82.5 μg/mL, P < 0.05). In the whole growth cycle of the mice, no significant difference in weight gain was observed in the single or double transgenic mice as compared with the na?ve mice (P>0.05). We successfully prepared GH/tPA double transgenic mice, in which GH gene transduction significantly increases the expression level of target gene tPA without affecting the growth and development of the transgenic mice. This success suggests a promising approach to preparing transgenic animals for producing pharmaceutical proteins and the breeding of the transgenic animals.

Mice with gene alterations in the GH and IGF family.

Much of our understanding of GH’s action stems from animal models and the generation and characterization of genetically altered or modified mice. Manipulation of genes in the GH/IGF1 family in animals started in 1982 when the first GH transgenic mice were produced. Since then, multiple laboratories have altered mouse DNA to globally disrupt Gh, Ghr, and other genes upstream or downstream of GH or its receptor. The ability to stay current with the various genetically manipulated mouse lines within the realm of GH/IGF1 research has been daunting. As such, this review attempts to consolidate and summarize the literature related to the initial characterization of many of the known gene-manipulated mice relating to the actions of GH, PRL and IGF1. We have organized the mouse lines by modifications made to constituents of the GH/IGF1 family either upstream or downstream of GHR or to the GHR itself. Available data on the effect of altered gene expression on growth, GH/IGF1 levels, body composition, reproduction, diabetes, metabolism, cancer, and aging are summarized. For the ease of finding this information, key words are highlighted in bold throughout the main text for each mouse line and this information is summarized in Tables 1, 2, 3 and 4. Most importantly, the collective data derived from and reported for these mice have enhanced our understanding of GH action.

Relationship of Growth Hormone Gene with Some physiological Characteristics of Common carp Cprinus carpio.L

This study was carried out at Al-Radhwaniyah Fish Reservoir (Baghdad) for the period from 16/9/2016 to 16/2/2017 to investigate the polymorphism of GH Gene and Relationship with glucose, cholesterol, AST, ALT, HDL and LDL in common carp. Single nucleotide polymorphism (SNPs) in GH gene was analyzed by direct sequencing. Results showed that there was a mutation in the site of G1217T, this SNP was significantly (p&lt;0.05) associated with the concentration of glucose and cholesterol in the blood. Heterozygote genotype (GT) recorded glucose concentration of 79.90 mg / 100ml while wild genotype (GG) 67.27 mg/100ml. Cholesterol reached 147.84 mg / 100 ml in GT genotype and 129.16 mg/100ml in GG genotype. The Results indicated was no significant associated with AST, ALT, HDL and LDL characteristics. The conclusion of this study, the polymorphism of GH gene is possible to adopt as a mark to predict the performance and selection of fish to be parents for future generations.K

Gamma-Aminobutyric Acid (GABA) Promotes Growth in Zebrafish Larvae by Inducing IGF-1 Expression via GABAA and GABAB Receptors.

Insulin-like growth factor-1 (IGF-1) primarily increases the release of gamma-aminobutyric acid (GABA) in neurons; moreover, it is responsible for the promotion of longitudinal growth in children and adolescents. Therefore, in this study, we investigated whether exogenous GABA supplementation activates IGF-mediated growth performance. Zebrafish larvae treated with GABA at three days post fertilization (dpf) showed a significant increase in the total body length from 6 to 12 dpf through upregulation of growth-stimulating genes, including IGF-1, growth hormone-1 (GH-1), growth hormone receptor-1 (GHR-1), and cholecystokinin A (CCKA). In particular, at 9 dpf, GABA increased total body length from 3.60 ± 0.02 to 3.79 ± 0.03, 3.89 ± 0.02, and 3.92 ± 0.04 mm at concentrations of 6.25, 12.5, and 25 mM, and the effect of GABA at 25 mM was comparable to 4 mM β-glycerophosphate (GP)-treated larvae (3.98 ± 0.02 mm). Additionally, the highest concentration of GABA (50 mM) -induced death in 50% zebrafish larvae at 12 dpf. GABA also enhanced IGF-1 expression and secretion in preosteoblast MC3T3-E1 cells, concomitant with high levels of the IGF-1 receptor gene (IGF-1R). In zebrafish larvae, the GABA-induced growth rate was remarkably decreased in the presence of an IGF-1R inhibitor, picropodophyllin (PPP), which indicates that GABA-induced IGF-1 enhances growth rate via IGF-1R. Furthermore, we investigated the effect of GABA receptors on growth performance along with IGF-1 activation. Inhibitors of GABAA and GABAB receptors, namely bicuculline and CGP 46381, respectively, considerably inhibited GABA-induced growth rate in zebrafish larvae accompanied by a marked decrease in the expression of growth-stimulating genes, including IGF-1, GH-1, GHR-1, and CCKA, but not with an inhibitor of GABAC receptor, TPMPA. Additionally, IGF-1 and IGF-1R expression was impaired in bicuculline and CGP 46381-treated MC3T3-E1 cells, but not in the cells treated with TPMPA. Furthermore, treatment with bicuculline and CGP 46381 significantly downregulated GABA-induced IGF-1 release in MC3T3-E1 cells. These data indicate that GABA stimulates IGF-1 release via GABAA and GABAB receptors and leads to growth promotion performance via IGF-1R.

PSVI-21 Fatty acid composition of blood lipids in lambs of different genotypes in ontogeny

Abstract The early period of postnatal ontogeny of sheep is characterized by a variety of metabolic processes that result in the formation and consolidation of a certain type of metabolism. A special role is played by lipids, which together with proteins and carbohydrates constitute the bulk of organic compounds, cells and the organism as a whole. The purpose of this research was to study the polymorphism of CAST and GH genes as well as its association with the fatty acid composition of blood plasma lipids in lambs. The content of fatty acids was determined by gas-liquid chromatography in the form of methyl esters. From the data obtained, it follows that in all studied ontogeny periods the peripheral blood of sheep with CASTNN and CASTMM genotypes had a higher concentration of fatty acids such as palmitic, stearic, linoleic, and arachidonic acids. The content is as follows: 27.58, 45.40, 3.16, 0.28% vs. 26.21, 45.31, 3.62, 0.18% at the age of 2 months; 25.07, 43.25, 6.05, 1.74% vs. 23.24, 38.76, 6.49, 1.32% at the age of 4 months; 20.64, 22.26, 14.17, 3.38% vs. 17.64, 19.91, 15.07, 2.46% at the age of 8 months (P ˂ 0.05), (P ˂ 0.01). Studies of blood lipid composition of GHBBand GHAA genotype carriers showed that palmitic, stearic, linoleic, and arachidonic acids were dominant: 27.95, 27.96, 19.04% vs. 26.08, 23.88, 17.56% at the age of 2 months, 46.87, 39.87, 22.37% vs. 3.24, 6.87, 15.56% at the age of 4 months; 0.45, 1.68, 3.81% vs. 0.29, 1.29, 3.19% at the age of 8 months (P ˂ 0.05), (P ˂ 0.01). Thus, this study emphasizes that there is a close relationship between the ratio of fatty acids in total blood lipids in lambs and the intensity of growth and development, ensuring and controlling the direction of biochemical processes in the growth and development of young sheep.

Plasmin generates vasoinhibin-like peptides by cleaving prolactin and placental lactogen

Vasoinhibin is an antiangiogenic, profibrinolytic peptide generated by the proteolytic cleavage of the pituitary hormone prolactin by cathepsin D, matrix metalloproteinases, and bone morphogenetic protein-1. Vasoinhibin can also be generated when placental lactogen or growth hormone are enzymatically cleaved. Here, it is investigated whether plasmin cleaves human prolactin and placental lactogen to generate vasoinhibin-like peptides. Co-incubation of prolactin and placental lactogen with plasmin was performed and analyzed by gel electrophoresis and Western blotting. Mass spectrometric analyses were carried out for sequence validation and precise cleavage site identification. The cleavage sites responsible for the generation of the vasoinhibin-like peptides were located at K170-E171 in prolactin and R160-T161 in placental lactogen. Various genetic variants of the human prolactin and placental lactogen genes are projected to affect proteolytic generation of the vasoinhibin-like peptides. The endogenous counterparts of the vasoinhibin-like peptides generated by plasmin may represent vasoinhibin-isoforms with inhibitory effects on vasculature and coagulation.

Association study between relative expression levels of eight genes and growth rate in Hungarian common carp (Cyprinus carpio)

One of the most important issues in improving the competitiveness of the fish production sector is to improve the growth rate of fish. The genetic background to this trait is at present poorly understood. In this study, we compared the relative gene expression levels of the Akt1s1, FGF, GH, IGF1, MSTN, TLR2, TLR4 and TLR5 genes in blood in groups of common carps (Cyprinus carpio), which belonged to different growth types and phenotypes. Fish were divided into groups based on growth rate (normal group: n = 6; slow group: n = 6) and phenotype (scaled group: n = 6; mirror group: n = 6). In the first 18 weeks, we measured significant differences (p < 0.05) between groups in terms of body weight and body length. Over the next 18 weeks, the fish in the slow group showed more intense development. In the same period, the slow group was characterized by lower expression levels for most genes, whereas GH and IGF1 mRNA levels were higher compared to the normal group. We found that phenotype was not a determining factor in differences of relative expression levels of the genes studied.

Estimation of the associations between GH and DGAT1 genes and growth traits by using decision tree in Awassi sheep

GH and DGAT1 are candidate genes associated with growth traits in sheep breeds. This study aims to determine the association between growth traits and GH and DGAT1 gene polymorphism using three statistical methods in Awassi sheep. The polymorphism was detected by the PCR-RFLP method. Three genotypes (AA, AB and BB) were observed for GH gene locus with allele and genotype frequency 0.70(A) and 0.30(B); 0.60(AA), 0.20(AB) and 0.20(BB). Three genotypes (CC, CT and TT) were found for DGAT1 gene locus with allele and genotype frequency 0.58(C) and 0.42(T); 0.47(CC), 0.23(CT) and 0.30(TT). The genes were in agreement with Hardy–Weinberg equilibrium (p > 0.05). CHAID, CRT and GLM were used to identify the association between growth traits and gene polymorphism. The results showed an association between GH locus and body weight and tail length. Also, found an association between DGAT1 locus and tail length. The three methods showed similar results in determining the association between genes and growth traits. Thus, the CHAID and CRT methods can evaluate the association between genes and growth traits.

The effects of 20-kDa human placental GH in male and female GH-deficient mice: an improved human GH?

A rare 20K isoform of GH-V (here abbreviated as GHv) was discovered in 1998. To date, only 1 research article has characterized this isoform in vivo, observing that GHv treatment in male high-fat fed rats had several GH-like activities, but unlike GH lacked diabetogenic and lactogenic activities and failed to increase IGF-1 or body length. Therefore, the current study was conducted to further characterize the in vivo activities of GHv in a separate species and in a GH-deficient model (GH-/- mice) and with both sexes represented. GHv-treated GH-/- mice had significant increases to serum IGF-1, femur length, body length, body weight, and lean body mass and reduced body fat mass similar to mice receiving GH treatment. GH treatment increased circulating insulin levels and impaired insulin sensitivity; in contrast, both measures were unchanged in GHv-treated mice. Since GHv lacks prolactin receptor (PRLR) binding activity, we tested the ability of GH and GHv to stimulate the proliferation of human cancer cell lines and found that GHv has a decreased proliferative response in cancers with high PRLR. Our findings demonstrate that GHv can stimulate insulin-like growth factor-1 and subsequent longitudinal body growth in GH-deficient mice similar to GH, but unlike GH, GHv promoted growth without inhibiting insulin action and without promoting the growth of PRLR-positive cancers in vitro. Thus, GHv may represent improvements to current GH therapies especially for individuals at risk for metabolic syndrome or PRLR-positive cancers.

Effect of dietary hydroxyproline supplementation on Chinese perch (Siniperca chuatsi) fed with fish meal partially replaced by fermented soybean meal

As a kind of biologically active molecule, hydroxyproline (Hyp) is abundant in fish meal (FM) but not in plant protein sources. It remains very challenging to replace FM with plant protein sources, particularly for carnivorous fish. This study aims to investigate the effect of dietary Hyp supplementation on Chinese perch (Siniperca chuatsi) fed with FM partially replaced by fermented soybean meal (FSM), with 46% FM as the positive control and 31% FM plus 15% FSM as the negative control. Based on the negative control diet, 0.5%, 1%, 1.5% and 2% of dietary crystal L-Hyp was supplemented to formulate four experimental diets, respectively. Although the replacement of 15% FM with FSM in the feed resulted in a significant decline in growth performance of Chinese perch, dietary supplementation of 1% Hyp could improve the growth performance with high mRNA levels of the gh and igf1 genes. Piecewise regression analysis revealed that a dietary level of 2.27% Hyp could achieve the maximum weight gain rate. With high mRNA levels of orexigenic genes (npy and agrp in the brain, and ghrelin in the gut) and low mRNA levels of anorexigenic genes (pomc and cart in the brain, and leptin-A in the liver), an appropriate level of Hyp could be added to the diet of Chinese perch as a food attractant to promote the appetite and increase food intake. Besides, partial replacement of FM with FSM might promote the deposition of amino acids in the muscle, which may not be affected by dietary supplementation of Hyp. Furthermore, dietary supplementation of Hyp affected the activity of prolyl hydroxylase (PHD) and the mRNA levels of type I collagen regulatory genes and coding genes of three prolyl 4-hydroxylase (P4H) isozymes in the muscle of Chinese perch to some extent. In addition, supplementation of an appropriate level of Hyp could significantly improve the collagen content and muscle quality (hardness, chewiness and springiness) of Chinese perch, which may greatly enhance its edible and nutritional values.

ИНДЕКС МОЛОЧНОСТИ КОРОВ С РАЗНЫМ ГЕНОТИПОМ

The live weight and milk production index of black-and-white and Tatarstan type cows of the Kholmogory breed with different genotypes for genes CSN3, DGAT1, PRL, GH were studied. It was found that cows with the homozygous genotype CSN3 AA, DGAT1 AA, PRL AA, GH LL are characterized by a high milk yield index. Unlike other marker genes, the somatotropin gene had a greater effect on the body weight and milk production index of cows. Thus, in terms of live weight in the black-and-white breed, the superiority of individuals with the GH LL genotype by 43 kg (P &lt;0.001), GH LV by 42 kg (P &lt;0.001) was noted, and in terms of milk production, the advantage of cows with the GH LL genotype (984 and 1008) over GH LV by 40 (P &lt;0.01); on the Kholmogory breed above GH LV by 26 (P &lt;0.05), GH VV by 42 (P &lt;0.05). Consequently, cows with allelic A variant of the CSN3, DGAT1, PRL genes and allelic L GH genes in their genomes exhibit high milk production at optimal live weight.

Isolated growth hormone deficiency type IA due to a novel GH1 variant: a case report

BackgroundA case of isolated growth hormone deficiency type IA (IGHD IA) caused by novel compound heterozygous mutation in the GH1 gene was reported in this study, which aimed to provide insights that will benefit future diagnosis and treatment.Case presentationWe analyzed and summarized the clinical data and genetic test results from a patient with IGHD admitted in March 2019 to the Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. We described the results from a 1-year-9-months old female, whose chief complaint was “growth retardation for more than one year”. Her birth length was 49.0 cm, and her birth weight was 3.05 kg. Suboptimal intake (breastfeeding) jaundice lasted for approximately two months following birth. When evaluated at the age of 1-year-9-months old, the patient’s height was 61.0 cm (− 7.24 SD), and her weight was 6.4 kg (− 1.50 SD). The patient’s physical characteristics included yellowish hair, large and unclosed anterior fontanelles, raised forehead, and a low and flat nose. The major abnormalities observed from the auxiliary examinations included low GH (< 0.05 μg/l), low IGF-1 (16.99 μg/l), and elevated TSH (6.97 mIU/l). Genetic testing revealed two heterozygous variants: a splicing mutation (NG_011676.1(NM_022560.4): c.10 + 1G>T, inherited from her mother) in intron 1 of the GH1 gene and a deletion that encompassed the same gene (chr17: 61973811–61996255, inherited from her father). After hormone replacement therapy with L-thyroxine and recombinant human GH (rhGH), the patient’s thyroid function returned to normal, and her serum IGF-1 level significantly improved, which resulted in an accelerated increase in height.ConclusionThis study described a case of IGHD caused by novel compound heterozygous mutations in the GH1 gene. This study suggested that closer attention should be directed to genetic testing and diagnosis based on clinical characteristics to avoid misdiagnosis.

Генетична основа ендокринної патології

Метою наведеного огляду був аналіз даних літератури щодо молекулярно-генетичної основи та діагностики ендокринної патології. Проведено огляд наукової літератури за ключовими словами «гени», «ендокринні хвороби», «молекулярна діагностика», «прогормони», «ядерні рецептори і фактори транс­крипції» з використанням пошукової системи PubMed. Беручи до уваги дослідження, проведені в останні 10 років, проаналізовані тези 144 статей. Більш детально вивчено результати дослідження, висвітлені у 32 статтях. Серед наведених нозологій — різні спадкові форми гіпопітуїтаризму, порушення біосинтезу стероїдних гормонів, порушення формування статі, моногенні форми цукрового діабету (ЦД) та інші захворювання. Виділено патологію, що пов’язана з мутацією генів, які кодують білкові прогормони, рецептори, ферменти біосинтезу стероїдів, молекули внутрішньоклітинного сигналінгу, транспортні білки, іонні канали, фактори транскрипції. Серед ендокринних захворювань, асоційованих із дефектами генів, які кодують білкові прогормони, найбільш поширеними є дефекти гена GH1; серед захворювань, асоційованих із дефектами генів, які кодують ферменти, найбільш поширеними є дефекти гена CYP21A2 (21-гідроксилази). Частіше мутації генів, які кодують білки, що відносяться до класу рецепторів, пов’язані із G-білком (G-protein coupled receptors). Більшість мутацій, пов’язаних із МЕН-2А, зосереджено в багатому цистеїном регіоні рецептора Ret. Відомо більше 70 моногенних синдромів, при яких відзначається клінічно виражена толерантність до глюкози і діагностується та чи інша форма ЦД, також виявлений ЦД, зумовлений мутацією мітохондріального гена (мутація tRNALeu, UUR). Самою частою з усіх моногенних форм є ожиріння, спричинене мутацією гена рецептора меланокортину 4-го типу (MC4R). У хворих на вроджений гіпотиреоз підвищена частота алелей HLA (Bw44, Aw24, B18) та описані мутації в генах TITF1, TITF2, FOXE1, PAX8 (транскрипційні маркери нормального онтогенезу щитоподібної залози).

Mutations in GH1 gene and isolated growth hormone deficiency (IGHD): A familial case of IGHD type I and systematic review

BackgroundIsolated growth hormone deficiency (IGHD) due to mutations in GH1 gene is a rare disease caused by deficient production of endogenous growth hormone (GH). MethodsWe reported the clinical manifestation and genetic diagnosis (whole exome sequencing [WES], nested PCR Sanger sequencing, and rtPCR) of a family with two children with IGHD type I. We conducted a systematic review of cases with IGHD and compared height, and treatment outcomes in subtypes of IGHD. ResultsThe patients were siblings born of nonconsanguineous parents from the Chinese Han population. The siblings both presented significantly short stature without other apparent abnormalities. The patients carry compound heterozygous mutations in GH1: a deletion and c.456 + 1G > A mutation that led to abnormal splicing. The systematic review identified 365 IGHD cases with GH1 mutations. Among these patients, their body height was most severely impaired in patients with IGHD type Ia, and the height standard deviation score decreased with the age of diagnosis in IGHD type Ia. Patients with IGHD type II had the longest duration of rhGH treatment, while patients with IGHD type Ib had the highest relative height improvement. ConclusionWe identified two patients with IGHD type I caused by compound heterozygotic GH1 deletion and splicing mutation. The analysis of previously published IGHD patients suggests differences in linear growth among subtypes of IGHD.