Tall Stature Research Articles

FRI307 Gigantism Due To Transcriptional Activation Of GHRH: The First Case Of Hormone-encoding Gene Overexpression Underlying A Congenital Disorder

Abstract Disclosure: A. Hattori: None. Y. Katoh-Fukui: None. R. Zhang: None. M. Terao: None. S. Takada: None. K. Nakabayashi: None. K. Hata: None. Y. Yamada: None. N. Matsuura: None. M. Fukami: None. Background: Pituitary gigantism is characterized by tall stature due to GH overproduction. To date, known genetic causes of pituitary gigantism are invariably associated with predispositions to tumors producing GH or GHRH. Clinical and genetic findings of the patient: The patient was a Japanese woman who was born mildly large for gestational age. Her overgrowth started in her first year of life. Despite radiation and pharmacotherapy starting at age three years, she reached an adult height of 197 cm (+7.4 SD). She developed panhypopituitarism associated with empty sella in adulthood and was deceased during sleep at age 53 years. Exome sequencing identified no pathogenic variant causing acromegaly or gigantism. Chromosomal microarray analysis detected a 752-kb deletion upstream of GHRH. This deletion was predicted to create a chimeric gene consisting of the 5´-UTR of TTI1, a ubiquitously expressed gene, and the coding region of GHRH. Reverse transcription PCR (RT-PCR) using mRNA of immortalized lymphoblastoid cells detected the chimeric transcript. Analysis of model mice: We established a mouse model harboring a 676-kb deletion upstream of Ghrh using the CRISPR/Cas9 system. RT-PCR detected a chimeric transcript consisting of the 5´-UTR of Tti1 and the coding region of Ghrh, which mimicked the patient’s chimeric transcript. Mutant mice started to overgrow at two weeks of age and showed high serum GH levels and long tibia at 12-13 weeks of age. Quantitative RT-PCR showed that the median level of Ghrh expression in the hypothalamus of the mutant mice was three-fold higher than that of the wildtype mice. Furthermore, the mutant mice had ectopic Ghrh expression in all analyzed tissues (the pituitary, thymus, heart, liver, and gonad). Discussion: Our findings propose a novel etiology of gigantism. In the present case, the GHRH gene obtained a constitutively active promoter through germline genomic microdeletion. The newly acquired promoter likely led to the constant expression of GHRH in various tissues including the hypothalamus. Possible explanations for GH overproduction in the present case include (1) GHRH overproduction in the hypothalamus, (2) paracrine and autocrine effects of GHRH secreted from the pituitary, and (3) endocrine effects of GHRH produced outside the hypothalamic-pituitary unit. The patient’s clinical course suggests that prenatal GHRH overproduction only mildly affects human growth. More importantly, this is the first case in which transcriptional activation of a hormone-encoding gene caused a human congenital disorder. Presentation: Friday, June 16, 2023

Associations between epigenome-wide DNA methylation and height-related traits among Sub-Saharan Africans: the RODAM study.

Human height and related traits are highly complex, and extensively research has shown that these traits are determined by both genetic and environmental factors. Such factors may partially affect these traits through epigenetic programing. Epigenetic programing is dynamic and plays an important role in controlling gene expression and cell differentiation during (early) development. DNA methylation (DNAm) is the most commonly studied epigenetic feature. In this study we conducted an epigenome-wide DNAm association analysis on height-related traits in a Sub-Saharan African population, in order to detect DNAm biomarkers across four height-related traits. DNAm profiles were acquired in whole blood samples of 704 Ghanaians, sourced from the Research on Obesity and Diabetes among African Migrants study, using the Illumina Infinium HumanMethylation450 BeadChip. Linear models were fitted to detect differentially methylated positions (DMPs) and regions (DMRs) associated with height, leg-to-height ratio (LHR), leg length, and sitting height. No epigenome-wide significant DMPs were recorded. However we did observe among our top DMPs five informative probes associated with the height-related traits: cg26905768 (leg length), cg13268132 (leg length), cg19776793 (height), cg23072383 (LHR), and cg24625894 (sitting height). All five DMPs are annotated to genes whose functions were linked to bone cell regulation and development. DMR analysis identified overlapping DMRs within the gene body of HLA-DPB1 gene, and the HOXA gene cluster. In this first epigenome-wide association studies of these traits, our findings suggest DNAm associations with height-related heights, and might influence development and maintenance of these traits. Further studies are needed to replicate our findings, and to elucidate the molecular mechanism underlying human height-related traits.

BIOMETRIC INDICES OF POLLEN FROM NATURAL POPULATIONS OF <i>PINUS BRUTIA</i> VAR. <i>PITYUSA</i> (PINACEAE) OF THE CRIMEAN MOUNTAINS

The study of biometric characteristics of Pinus brutia var. pityusa pollen was carried out in natural populations of P. brutia var. pityusa in the Crimean Mountains. The pollen was collected during the period of its free flight on sample plots along four hypsometric profiles. In the western part of the southern macroslope of the Main Ridge of the Crimean Mountains on Cape Aya in the Ayazma tract, 3 sample plots were laid at altitudes of 50–290 m above sea level, in Batiliman – 2 plots, at altitudes of 50 and 120 m above sea level; in the eastern part of the macroslope, 3 plots were laid on Karaul-Oba Mt. at altitudes of 40–120 m above sea level, and in the Novyy Svet tract – 2 plots at 50 and 100 m above sea level. Biometric analysis of pollen grains was carried out on temporary acetocarmine slides using generally accepted methods. The results of the study showed that an average size of the pollen grain of P. brutia var. pityusa in natural populations of the Crimean Mountains varies within the following ranges: total grain length from 81.5 to 88.5 μm, the length and height of the pollen grain body 52.2–59.4 μm and 47.8–53.4 μm, respectively, and the length and height of the air sac 40.0–43.0 μm and 25.5–30.4 μm, respectively. The smallest pollen is formed in coastal stands. In the plantations of P. brutia var. pityusa in the western part of the Crimean Mountains, a decrease in the length and height of the air sacs was noted. It was revealed that the indices characterizing the ratio of individual structural elements of the pollen grain, namely γ – the ratio of the body length to the height of the air sac of the pollen grain, δ – the ratio of the body height to the height of the air sac, and Θ – the ratio of the body length to the length of the air sac, allow to analyze aerodynamic properties of P. brutia var. pityusa pollen. The decrease in γ, δ, and Θ pollen indices in the plantations of Ayazma and Batiliman reflects a decrease in the efficiency of its aerial distribution, which has a negative effect on the level of heterogeneity of natural populations in these territories.

Trends in women's height and the effect of early childbearing on height retardation: An analysis of the height of Bangladeshi women born between 1974 and 1998.

Depending on race, ethnicity, and region, genetic variants determine human height by 65% to 80%, while the remaining variance of 20% to 35% is influenced by nutrition and other individual or environmental exposures in the early years of life. An improvement in nutrition and health in the early years in a population underprivileged in health and nutrition will likely increase the group's average height. Due to outstanding improvements in these areas in recent decades, we hypothesised that the average height of Bangladeshi women has increased. Moreover, because pregnancy at an early age affects women's health and nutrition, we hypothesised that women who began childbearing early would experience growth retardation compared to women who had pregnancies at a later age. We used data from five national surveys conducted between 2004 and 2018 that collected height data from ever-married women aged 15-49 years. We analysed the height of women aged 20-29 years (born between 1974 and 1998) and examined the mean height by birth years, age at first birth (AFB), economic status, religion and region. We conducted multiple linear regression models, controlling for the differential effects of the socio-demographic characteristics on women's height over time and by AFB. The average height of women born between 1974 and 1998 significantly increased by 0.03 cm annually, with fluctuations between 150.3 and 151.6 cm. We also found an association between age at childbearing and height in adulthood - women who began childbearing before age 17 were approximately one centimetre shorter in adulthood than those who began childbearing at a later age. We found evidence of an increasing trend in women's height in Bangladesh and an inhibiting effect of early teenage childbearing on attaining the potential growth of women. The findings call for further studies to investigate early childbearing and its consequences on women's and their children's growth in diverse settings, considering socio-cultural customs influencing early marriage and childbearing.

Tall stature and the combination risk on kidney damage with overweight and lifestyle among the diabetic population

Tall stature and the combination risk on kidney damage with overweight and lifestyle among the diabetic population

A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry.

To investigate whether there is an influence on the results of lumbar spine bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) under three different hip flexion angles (90°, 45°, 0° of hip flexion). We collected a total of 60 outpatients, including 44 females (56.4 ± 5.7 years) and 16 males (50.2 ± 13.7 years). The DXA results of the lumbar spine were scanned and analyzed in three different positions with hip flexion of 90°, 45°, and 0°. We found that there was no significant difference in the area of interest, bone mineral content, BMD, and vertebral body height of the lumbar vertebral body measured by DXA in three hip flexion positions of 90°, 45°, and 0°; Pearson's correlation analysis showed that lumbar BMD in hip flexion 90° was correlated with it in hip flexion 45° (r = 0.998, P＜0.01) and in hip flexion 0° (r = 0.996, P＜0.01) respectively. There was no statistically significant difference in the diagnosis of BMD between 90° and 45° hip flexion (P = 0.903), which was the same as 90° and 0° hip flexion (P = 0.822). Therefore, we conclude that different hip flexion angles can be used in lumbar BMD detection by DXA, which is beneficial to patients who have difficulty in hip flexion, especially for elderly patients with osteoporosis.

An innovative method for human height estimation combining video images and 3D laser scanning.

Digitalization has increased the number of video surveillance systems that sometimes capture crime images. Traditional methods of human height estimation use projective geometry. However, sometimes they cannot be used because the video camera surveillance system is not available or has been moved and there are no reference lines on the frame. Scientific studies have developed a new method for human height estimation using 3D laser scanning. This model necessarily requires a series of approximations, which increase the final measurement error. To overcome this problem, in the present study, images of a subject are projected directly on the 3D model, estimating the height of the subject. This article describes the methodological approach adopted through the analysis of a real case study in a controlled environment executed by Carabinieri Forensic Investigation Department (Italy). The aim is to obtain a human anthropometric measure derived from frames extracted from the videos associated with the digital survey of the framed area obtained with 3D laser scanning and point cloud analysis. The result is the height estimation of five subjects filmed by a camera obtained through the combination of 2D images extracted by a DVR/surveillance systems with 3D laser scanning. Results show that most estimated measurements are less than the real measurement of the subject; it also depends on the posture of the subject while walking. Furthermore, results shows the differences between the real height and the estimated height with a statistical approach.

Virtual cone-beam computed tomography simulator with human phantom library and its application to the elemental material decomposition

PurposeThe purpose of this study is to develop a virtual CBCT simulator with a head and neck (HN) human phantom library and to demonstrate the feasibility of elemental material decomposition (EMD) for quantitative CBCT imaging using this virtual simulator. MethodsThe library of 36 HN human phantoms were developed by extending the ICRP 110 adult phantoms based on human age, height, and weight statistics. To create the CBCT database for the library, a virtual CBCT simulator that simulated the direct and scattered X-ray on a flat panel detector using ray-tracing and deep-learning (DL) models was used. Gaussian distributed noise was also included on the flat panel detector, which was evaluated using a real CBCT system. The usefulness of the virtual CBCT system was demonstrated through the application of the developed DL-based EMD model for case involving virtual phantom and real patient. ResultsThe virtual simulator could generate various virtual CBCT images based on the human phantom library, and the prediction of the EMD could be successfully performed by preparing the CBCT database from the proposed virtual system, even for a real patient. The CBCT image degradation owing to the scattered X-ray and the statistical noise affected the prediction accuracy, although these effects were minimal. Furthermore, the elemental distribution using the real CBCT image was also predictable. ConclusionsThis study demonstrated the potential of using computer vision for medical data preparation and analysis, which could have important implications for improving patient outcomes, especially in adaptive radiation therapy.

TGF-β and BMP Signaling Pathways in Skeletal Dysplasia with Short and Tall Stature.

The transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways play a pivotal role in bone development and skeletal health. More than 30 different types of skeletal dysplasia are now known to be caused by pathogenic variants in genes that belong to the TGF-β superfamily and/or regulate TGF-β/BMP bioavailability. This review describes the latest advances in skeletal dysplasia that is due to impaired TGF-β/BMP signaling and results in short stature (acromelic dysplasia and cardiospondylocarpofacial syndrome) or tall stature (Marfan syndrome). We thoroughly describe the clinical features of the patients, the underlying genetic findings, and the pathomolecular mechanisms leading to disease, which have been investigated mainly using patient-derived skin fibroblasts and mouse models. Although no pharmacological treatment is yet available for skeletal dysplasia due to impaired TGF-β/BMP signaling, in recent years advances in the use of drugs targeting TGF-β have been made, and we also discuss these advances.

DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)—height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children’s SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC.

Letter to the Editor Regarding “Comparison of Commonly Used Methods to Predict the Final Height in Constitutional Tall Stature”

Letter to the Editor Regarding “Comparison of Commonly Used Methods to Predict the Final Height in Constitutional Tall Stature”

Probing the Relationship Between the Human Gut Microbiome and Prospects of Prostate Cancer: A Systematic Review.

Prostate neoplasia is one of the most commonly occurring neoplasias in males and has a high mortality rate. Prostate cancer (PCA) risk factors include tall stature, male sex, known family history, obesity, high blood pressure, lack of fitness, higher levels of testosterone for a long time, increasing age, and ethnicity are well known. The association and role of the gut microbiota in different diseases in our body have been highlighted recently. Therefore, finding the influence of gut microbiota on the prostatic cells can be useful for preventing prostatic neoplasia and/or reducing its severity. We aimed to assess its impact on PCA risk. We thoroughly searched databases for the relevant literature for our systematic review. The final research papers analyzed how bacteria played a role in the risk of PCA, either through inflammation or the production of metabolites that increase/decrease the risk of PCA. Based on the studies reviewed, we found that some gut bacteria play a role in the formation of PCA. In contrast, some bacteria can help prevent PCA, but the metabolism of the dietary components is the major factor for PCA.

The influencing factors and an error correction method of the use of infrared thermography in human facial skin temperature

This study analyzed the influencing factors of the thermal infrared imager's measurement of facial skin temperature based on infrared radiation theory, temperature measurement principle, and a proposed simplified operation range estimation method. Climate-controlled experiments were carried out to determine the influencing factors further. The experiments include nine temperature levels (12, 15, 18, 21, 24, 26, 28, 30, and 32 °C), three target-object distances (1,2 and 3 m), and two view angles (0° and 38.7°). A total of 866 valid samples from 40 participants were collected. The results revealed that the factors influencing operation range are the specifications of the infrared camera and human body height. The main factors impacting measurement are the measured skin temperature, the surrounding air temperature and the position between the camera and the human. Among them, the measured skin and air temperatures contributed 54.3% and 26.7% to the measurement difference. Compared to the distance, the influencing degree of the angle is more prominent. Considering these factors, we proposed an error correction method. The correction results show that the mean difference is −0.01 °C (95% confidence interval is −0.19 to 0.17 °C) with the 95% limits of agreement (LoA) within ±0.53 °C, which significantly reduces the original measurement difference with the mean difference of −0.58 °C (95%LoA: ±1.31 °C). The results of this study provide a theoretical basis for providing high-quality facial skin temperature data when subsequent thermal infrared imagers are used in the human body.

Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma

IntroductionSeveral studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma. MethodsUsing genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted by case diagnosis age, metastasis status, tumor location, tumor histology, and presence of a known pathogenic variant in a cancer susceptibility gene. ResultsGenetically inferred higher birthweight was associated with an increased risk of osteosarcoma (OR =1.59, 95% CI 1.07–2.38, P = 0.02). This association was strongest in cases without metastatic disease (OR =2.46, 95% CI 1.44–4.19, P = 9.5 ×10-04). Although there was no overall association between osteosarcoma and genetically inferred taller stature (OR=1.06, 95% CI 0.96–1.17, P = 0.28), the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03–1.63, P = 0.03). There were no significant associations between the GRS for puberty timing and osteosarcoma. ConclusionA genetic propensity to higher birthweight was associated with increased osteosarcoma risk, suggesting that shared genetic factors or biological pathways that affect birthweight may contribute to osteosarcoma pathogenesis.

Recurrent Spontaneous Pneumothorax of Unknown Etiology in a Young Patient: Case Report

Introduction: Spontaneous pneumothorax is defined as the abnormal accumulation of air in the pleural space between the lungs and the chest wall, it occurs without an obvious etiology, such as trauma or iatrogenic causes. Primary spontaneous pneumothorax occurs when ther e is no history of underlying lung disease, while secondary spontaneous pneumothorax is associated with a history of underlying lung disease; its diagnosis is based on clinical suspicion and can be confirmed with imaging tests. Case presentation: We prese nt a 17 year old patient who presented spontaneous right pneumothorax, requiring placement of endopleural tube and Heimlich cannula with long stay, discharged for resolution and later relapsing in initial symptomatology one week later, requiring hospital readmission. Conclusion The recidivant spontaneous pneumothorax in the context of a young patient with clinical characteristics like those of our patient: tall stature, pectus excavatum, hyperlaxity of the integuments and aortic-mitral murmur, gives us hig h suspicion of a secondary cause, a good clinical history, with particular focus on the maternalfetal history and a detailed physical examination, are the most useful tools to integrate a diagnosis of connective tissue diseases.

When growth exceeds boundaries: Tall stature, enlarged hands & feet – Is it what you think?

No abstract available

Pyoderma gangrenosum with Marfan syndrome and Crohn’s disease: A rare association

A 22-year-old man presented with multiple, painful ulcers on the thighs, legs, and face of 10-day duration and diarrhea and bleeding per rectum of 2-year duration. The ulcers were tender and had a peripheral violaceous border. General examination revealed tall stature, long extremities, kyphosis, arachnodactyly, and hyperextensible wrist and thumbs. The arm span was more than the height and the thumb sign and wrist sign were positive, diagnostic of Marfan syndrome. Skin biopsy from the edge of the ulcer showed infiltrates of neutrophils and lymphocytes in the dermis and subcutaneous tissue. A detailed evaluation ruled out other causes for skin ulceration and we made a diagnosis of pyoderma gangrenosum. Echocardiogram demonstrated mitral valve prolapse. Computed tomography of abdomen showed segmental mucosal thickening as skip lesions in the colon and rectum. Endoscopy showed chronic colitis with multiple punched out ulcers. Colonic biopsy showed noncaseating granulomas suggestive of Crohn’s disease. Although inflammatory bowel disease is a well-known association of pyoderma gangrenosum, we did not come across any previous reports of coexistence of pyoderma gangrenosum, Crohn’s disease, and Marfan syndrome.

Effects of Stature and Load Carriage on the Running Biomechanics of Healthy Men.

Overuse musculoskeletal injuries, often precipitated by walking or running with heavy loads, are the leading cause of lost-duty days or discharge during basic combat training (BCT) in the U.S. military. The present study investigates the impact of stature and load carriage on the running biomechanics of men during BCT. We collected computed tomography images and motion-capture data for 21 young, healthy men of short, medium, and tall stature (n = 7 in each group) running with no load, an 11.3-kg load, and a 22.7-kg load. We then developed individualized musculoskeletal finite-element models to determine the running biomechanics for each participant under each condition, and used a probabilistic model to estimate the risk of tibial stress fracture during a 10-week BCT regimen. Under all load conditions, we found that the running biomechanics were not significantly different among the three stature groups. However, compared to no load, a 22.7-kg load significantly decreased the stride length, while significantly increasing the joint forces and moments at the lower extremities, as well as the tibial strain and stress-fracture risk. Load carriage but not stature significantly affected the running biomechanics of healthy men. We expect that the quantitative analysis reported here may help guide training regimens and reduce the risk of stress fracture.

Sex chromosome aneuploidies and fertility: 47,XXY, 47,XYY, 47,XXX, and 45,X/47,XXX.

The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, XXX, with special reference to the karyotype 45,X/47,XXX. Each has a "specific" (but variable) phenotype, but may be modified by mosaicism. Although the alterations in the hypothalamic-pituitary-gonadal axis are important (and discussed), the emphasis is on potential fertility. The reproductive axis is often affected in females with the 47,XXX karyotype with diminished ovarian reserve and accelerated loss of ovarian function. Fewer than 5 % of females with the Turner syndrome have the 45,X/47,XXX karyotype. They have taller stature and less severe fertility issues compared to females with the 45,X or other forms of Turner syndrome mosaicism. For the 47,XXY karyotype non-obstructive azoospermia is almost universal with sperm retrieval by micro-testicular sperm extraction possible in slightly fewer than half of the men. Men with the 47,XYY karyotype have normal to large testes and much less testicular dysfunction than those with the 47,XXY karyotype. They do have a slight increase in infertility compared to the reference population, but not nearly so severe as those with 47,XXY karyotype. Assisted reproductive technology, especially micro-TESE has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3-D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.

Rancang Bangun Alat Hitung Indeks Massa Tubuh Berbasis Arduino

This study aims to design Arduino-based scales for weight, height, body mass index. Height and weight measuring device is a measuring tool that functions to measure the height and weight of a person's body. To measure height and weight in general, it is still done separately (separately) in this case the measurements of height and weight are carried out using different tools. By increasing the pace of technological advances, especially in the health sector, according to the author's observations, the height and weight measuring devices are still manual, it's time to increase their function, in this case, it is necessary to increase the function of the tool, especially those related to the field of electronics. The results of measuring weight using CAMRY brand scales with Karya Nesa scales, the average error rate is 0.037 (still within the tolerance threshold), while the results of measuring height are in accordance with the actual. From the results of the Body Mass Index (BMI) analysis with the results of the Body Mass Index (BMI) measurement by Nesa, it is correct and valid (valid). The error rate of weight or scales is relatively small, the accuracy of the scales is very good. The error rate is declared large, if the error is above 5% or greater than 0.05. Based on the results obtained, it is suggested that the scales need to be made precise (not rocking), this can be harmful to the patient and needs to be developed by adding sounds such as: weight, height and BMI results