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Background: Hypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated. Methods: Here, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion. Results: Our patient's Xq28 deletion is 44,806 bp and contains only two genes, FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes (DEGs) in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier (SCB) regulation, apoptosis, inflammatory response, and gonadotropin-releasing regulation. Indeed, our patient has an elevated follicle stimulating hormone (FSH) level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation (XCI) is skewed toward the deleted X, suggesting a mechanism to avoid FSH dysregulation. Conclusion: Compared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and CMC4 results in dysregulation of apoptosis, inflammation, and FSH, and is sufficient to cause Xq28-associated HH.

Aim:The objective of the present study was to screen the anti-hyperglycaemic and antihyperlipidemic activities of leaf extracts (Pet-ether, Chloroform, Acetone, and Methanol) of Cassia glauca Lam. on streptozotocin-nicotinamide induced NIDDM rats. Methods: Acute oral toxicity of all extracts was carried out with a single dose of 2000 mg/kg in female non-pregnant albino Wistar rats. An oral glucose tolerance test was performed for all extracts in overnight fasted rats. The anti-hyperglycaemic and anti-hyperlipidemic activities were carried out on adult healthy albino Wistar rats of either sex. Diabetogenic drug Streptozotocin and Nicotinamide were administrated by intraperitoneal route. Standard drug glibenclamide was administered by the peroral route. Test drugs (extracts) were administered in doses of 200 mg/kg by the peroral route. Diabetic rats with serum glucose levels more than 250 mg/dl were selected for the study. Bodyweight, fasting serum glucose levels, and other biochemical parameters were monitored on the 1 st , 15 th , and 21 st day. Results: All four-leaf extract showed significant anti-hyperglycemic and lipid-lowering activity. Maximum activity was shown by methanolic extract (effect on FSGL=282.20±5.29 on day 1st to 139. 20±3.46 on 21 st day, p˂0.01), (effect on lipid parameters= (TG=105.69±0.71 on 15 th day to 110.19±0.70 on 21 st day, p˂0.01, CH=105.68±0.50 on 15 th day to 111.37±0.48 on 21 st day, p˂0.01 and S.HDL=37.29±0.22 on 15 th day to 38.05±0.44 on 21 st day, p˂0.01. Conclusion: From the present study a conclusion can be drawn that the methanolic extract of C. glauca leaves possesses potential anti-hyperglycaemic and anti-hyperlipidemic properties.

BackgroundHypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated.MethodsHere, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Furthermore, expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion.ResultsOur patient’s Xq28 deletion is 44,806bp and contains only two genes FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier regulation, apoptosis, inflammatory response and gonadotropin-releasing regulation. Indeed, our patient has an elevated FSH level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation is skewed towards the deleted X, suggesting a mechanism to avoid FSH dysregulation.ConclusionCompared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and/or CMC4 results in dysregulation of apoptosis, inflammation and FSH, and is sufficient to cause Xq28-associated HH.

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