A homozygous frameshift variant expands the clinical spectrum of SAMD9 gene defects.

SAMD9, a ubiquitously expressed protein, is involved in several mechanisms, including endosome fusion, growth suppression and modulation of innate immune responses to stress and viral infections. While biallelic mutations in SAMD9 are linked to normophosphatemic familial tumoral calcinosis, heterozygous gain-of-function mutations in the same gene are responsible for MIRAGE, a multisystemic syndrome characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. A two-and-a-half-year-old girl, from a consanguineous Lebanese family, was included in this study. She presents with pre- and post-natal growth retardation, recurrent fevers, persistent diarrhea, elevated CRP and intermittent hypoglycemia. Whole genome sequencing revealed a homozygous frameshift variant in SAMD9 (NM_017654.4: c.480_481del; p.Val162Ilefs*5) in the proband. Sanger sequencing confirms its segregation with the disease in the family, and immunoblotting showed that the detected variant abolishes SAMD9 expression in the patient. Our findings expand the clinical spectrum linked to SAMD9 and highlight the importance of investigating further cases with mutations in this gene, as this will pave the way towards the understanding of the pathways driving these diseases.

Gap in knowledge of health benefits and risks of combined oral contraceptives among Lebanese women.

BACKGROUND: Oral Contraceptive Pills (OCPs) are among the most commonly used forms of contraception, but they are associated with several health benefits and risks. This study aims to determine the gap in knowledge of the underlying health benefits and risks of OCPs among Lebanese women and to identify the factors that might influence their beliefs. METHODS: A questionnaire was completed by 817 Lebanese women aged 18-64 years old and assessed sociodemographic details, medical information, contraceptive practices, knowledge of underlying health benefits and risks, and information needs related to OCPs. RESULTS: Among the total participants, 41.5% of women reported using OCPs at some point in their lives yet 46.6% denied receiving information about their benefits and 48% denied receiving information about their risks. The mean total OCP knowledge score was 5.70 out of 25, the mean OCP risk knowledge score was 4.09 out of 15, and the mean OCP benefit knowledge score was 0.77 out of 6. Sociodemographic factors associated with greater total knowledge, risk knowledge and benefit knowledge included OCP usage, being a student, confidence in one's knowledge and satisfaction with one's information. Both the total and risk knowledge scores were found to be higher in women who found that receiving information related to OCPs was important. Finally, participants who lived in central governates had greater total knowledge scores, whereas those with higher levels of education and a family history of endometrial cancer demonstrated better benefit knowledge. CONCLUSIONS: This study highlighted the poor knowledge of health benefits and risks associated with OCP use among Lebanese women and the associated sociodemographic factors that might influence their beliefs.

Ghrelin hormone a new molecular modulator between obesity and glomerular damage.

The incidence of glomerular diseases is increasing worldwide due to increased prevalence of obesity which is a major risk factor for type-2 diabetes mellitus and cardiovascular disorders.Ghrelin, an orexigenic peptide hormone, has been implicated in obesity, and its impact on the pathology and function of the kidneys was found to be significant. Ghrelin known to regulate energy homeostasis and growth hormone release, has been shown to modulate critical signaling pathways involved in the health and survival of podocytes. These derangements directly affect glomerular function and manifest as impaired glomerular filtration barrier and leakage of albumin into urine. Although the pathological features of the above-mentioned disorders are different, they interestingly lead to similar clinical features of glomerular damage. The pathological events are majorly initiated by endocrine imbalance leading to abnormal activation of downstream signaling pathways involved in the development of glomerulosclerosis. In fact, obesity increases the risk of developing chronic kidney disease by altering the secretion of pro-inflammatory cytokines and adipokines, activating the renin-angiotensin-aldosterone system (RAAS), promoting lipotoxicity, oxidative stress and fibrosis within the kidneys. Whilst these bioregulators are well described, their direct involvement in renal homeostasis is still mostly elusive. This review summarized previous and recent evidence on the endocrine properties of ghrelin and perivascular adipose tissue involved in modulating kidney physiology.