Gonadal Failure in a Male With 3-M Syndrome

OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome

Gonadal Failure in a Male With 3-M Syndrome

OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome

Family and Population-Based Studies of Variation within the Ghrelin Receptor Locus in Relation to Measures of Obesity

The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites.In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p<0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 27+/-4 kg/m(2)) versus non-carriers (mean BMI: 28+/-5 kg/m(2)) (p>0.05) could be shown.In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies

Glucose homeostasis and insulin resistance: prevalence, gender differences and predictors in adolescents

BACKGROUND: Adolescence, due to transient pubertal insulin resistance (IR), is associated with a higher risk for disturbances of glucose metabolism. The aim of our study was 1) to investigate the prevalence of disturbances of glucose metabolism, 2) to define gender specific homeostasis model assessment of insulin resistance (HOMA-IR) thresholds associated with increased cardiometabolic risks and 3) to provide predictors of HOMA-IR. METHODS: The studied cohort consisted of Czech adolescents aged 13.0-17.9 years: 1,518 individuals of general population and three studied groups according weight category (615 normal weight, 230 overweight and 683 obese). The prevalence of IR, impaired fasting glucose (IFG) and type 2 diabetes was assessed. Risky HOMA-IR thresholds based on components of metabolic syndrome were investigated. HOMA-IR prediction was calculated taking into account age, blood pressure, multiple anthropometric, biochemical and hormonal parameters. RESULTS: In general population cohort, the prevalence of IFG and type 2 diabetes was 7.0% and <0.5%, respectively. Boys regardless of weight presented significantly higher levels of blood glucose and higher prevalence of IFG than girls. Obese boys were found more insulin resistant than obese girls. HOMA-IR thresholds of 3.6 for girls and 4.4 for boys were associated with increased cardiometabolic risks. For both genders, the model of HOMA-IR prediction was composed of age, BMI, ratio of free triiodthyronine to free thyroxine, gamma-glutamyltransferase activity and levels of triglycerides and sex hormone-binding globulin. CONCLUSIONS: The type 2 diabetes in adolescents, including those who were obese, was rarely diagnosed. Obese adolescent boys were at greater risk for IR and for IFG than obese girls. In adolescence, thresholds of HOMA-IR in contrast to predictors were found gender specific