VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.

Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated hypoxia signaling and a tumor microenvironment (TME) highly enriched in myeloid and lymphoid cells. Loss of the von Hippel Lindau (VHL) gene is a critical early event in ccRCC pathogenesis and promotes stabilization of HIF. Whether VHL loss in cancer cells affects immune cells in the TME remains unclear. Using Vhl WT and Vhl-KO in vivo murine kidney cancer Renca models, we found that Vhl-KO tumors were more infiltrated by immune cells. Tumor-associated macrophages (TAMs) from Vhl-deficient tumors demonstrated enhanced in vivo glucose consumption, phagocytosis, and inflammatory transcriptional signatures, whereas lymphocytes from Vhl-KO tumors showed reduced activation and a lower response to anti-programmed cell death 1 (anti-PD-1) therapy in vivo. The chemokine CX3CL1 was highly expressed in human ccRCC tumors and was associated with Vhl deficiency. Deletion of Cx3cl1 in cancer cells decreased myeloid cell infiltration associated with Vhl loss to provide a mechanism by which Vhl loss may have contributed to the altered immune landscape. Here, we identify cancer cell-specific genetic features that drove environmental reprogramming and shaped the tumor immune landscape, with therapeutic implications for the treatment of ccRCC.

Populism, Economic Distress, Cultural Backlash, and Identity Threat: Integrating Patterns and Testing Cross-National Validity.

Populism is on the rise across liberal democracies. The sociopsychological underpinnings of this increasing endorsement of populist ideology should be uncovered. In an online cross-sectional survey study among adult samples from five countries (Chile, France, Italy, Romania, and the United Kingdom; N = 9,105), we aimed to replicate an economic distress pattern in which relative deprivation and identity threat are associated with populism. We further tested a cultural backlash pattern-including perceived anomie, collective narcissism, and identity threat as predictors of populism. Multigroup structural equation models supported both economic distress and cultural backlash paths as predictors of populist thin ideology endorsement. In both paths, identity threat to belonging played a significant role as partial mediator. Furthermore, an integrative model showed that the two patterns were not mutually exclusive. These findings emphasize the implication of identity threat to belonging as an explanatory mediator and demonstrate the cross-national generalizability of these patterns.

Happiness Maximization Is a WEIRD Way of Living.

Psychological science tends to treat subjective well-being and happiness synonymously. We start from the assumption that subjective well-being is more than being happy to ask the fundamental question: What is the ideal level of happiness? From a cross-cultural perspective, we propose that the idealization of attaining maximum levels of happiness may be especially characteristic of Western, educated, industrial, rich, and democratic (WEIRD) societies but less so for others. Searching for an explanation for why "happiness maximization" might have emerged in these societies, we turn to studies linking cultures to their eco-environmental habitat. We discuss the premise that WEIRD cultures emerged in an exceptionally benign ecological habitat (i.e., faced relatively light existential pressures compared with other regions). We review the influence of the Gulf Stream on the Northwestern European climate as a source of these comparatively benign geographical conditions. We propose that the ecological conditions in which WEIRD societies emerged afforded them a basis to endorse happiness as a value and to idealize attaining its maximum level. To provide a nomological network for happiness maximization, we also studied some of its potential side effects, namely alcohol and drug consumption and abuse and the prevalence of mania. To evaluate our hypothesis, we reanalyze data from two large-scale studies on ideal levels of personal life satisfaction-the most common operationalization of happiness in psychology-involving respondents from 61 countries. We conclude that societies whose members seek to maximize happiness tend to be characterized as WEIRD, and generalizing this across societies can prove problematic if adopted at the ideological and policy level.

Making Digital Health Equitable.

Most agree that the current healthcare system is broken. Fortunately, technology is increasing at an exponential rate and provides a solution for the future. Digital Health is an integrator concept that has the potential to take advantage of technological advantages. Digital Health converges health, healthcare, research, and everyday life. It includes technologies, platforms, and systems that engage consumers in all aspects of life. It makes health and healthcare be people-centered and personalized. Digital health requires total interoperability - standards, common data elements, and the integration of data from all sources. It demands data sharing. Digital Health brings together a wide range of stakeholders for similar goals using the same resources. Digital Health uses mobile devices and wearable sensors and uses Artificial Intelligence and Machine Learning to handle the vast amount of data Digital Health engages. Finally, Digital Health has the potential to open the gap between the different social and economic classes that must be addressed.

WEIRD-Confucian comparisons: Ongoing cultural biases in psychology's evidence base and some recommendations for improving global representation.

The realization that most behavioral science research focuses on cultures labeled as WEIRD-Western, educated, industrialized, rich, and democratic (Arnett, 2008; Henrich et al., 2010; Thalmayer et al., 2021)-has given an impetus to extend the research to more diverse populations. Confucian East Asian societies have relatively strong social and technological infrastructure to advance science and thus have gained much prominence in cross-cultural studies. This has inadvertently fostered another bias: the dominance of WEIRD-Confucian comparisons and a tendency to draw conclusions about "non-WEIRD" cultures in general based on data from Confucian societies. Here, analyzing 1,466,019 scientific abstracts and, separately, coverage of 60 large-scale cross-cultural psychological projects (Nsamples = 2,668 from Ncountries = 153 covering nparticipants = 3,722,940), we quantify the dominance of Confucian over other non-WEIRD cultures in psychological research. Our analysis also reveals the underrepresentation of non-European Union postcommunist societies and the almost total invisibility of Pacific Island, Caribbean, Middle African, and Central Asian societies within the research database of psychology. We call for a shift in cross-cultural studies toward midsize (7+ countries) and ideally large-scale (50+ countries) cross-cultural studies, and we propose mitigations that we believe could aid the inclusion of diverse researchers as well as participants from underrepresented cultures in our field. People in all world regions and cultures deserve psychological knowledge that applies to them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Role of Lymphovascular Invasion in Oral Cavity Squamous Cell Carcinoma Regional Metastasis and Prognosis.

OBJECTIVE: The overall 5-year survival for oral squamous cell carcinoma (OSCC) has not changed in the last 20 years despite advances in treatment. Lymphovascular invasion (LVI) has been shown to be a negative prognostic factor in other cancers, however its role in the prognosis of OSCC remains unclear. This study aims to determine if LVI is a predictor of cervical lymph node metastasis and/or recurrence in OSCC. METHODS: We conducted a retrospective cohort review of patients from our institutional cancer registry who were treated for OSCC between 2004 and 2018. Patient demographics, surgical pathology results, and clinical outcome data were collected. A multivariable logistic regression analysis was performed to determine if LVI was an independent predictor of cervical lymph node metastasis and/or recurrence. RESULTS: 442 patients were included, 32.8% were female and median age at time of diagnosis was 61.2 years. LVI was present in 32.8% of patients. When controlled for age, sex, t-classification, perineural invasion, depth of invasion (DOI), and margin status, LVI was a significant predictor of the presence of cervical node metastasis (OR: 3.42, CI: 2.17-5.39, P < .001). There was no significant association found between LVI and local recurrence (OR: 1.03, CI: 0.57-1.84, P = .92), regional recurrence (OR: 1.10, CI: 0.57-2.11, P = .78), or distant recurrence (OR: 1.59, CI: 0.87-2.94, P = .13). CONCLUSION: The results of this study suggest that LVI is a significant predictor of the presence of cervical lymph node metastasis at presentation independent of other known prognostic factors. LVI, however, was not found to be a significant independent predictor of locoregional or distant recurrence.Level of Evidence: Level III.

Evaluating skills for psychological recovery with gunshot injury survivors in a hospital-based early intervention program.

Gun violence is a serious public health problem that places surviving victims at increased risk for a variety of mental health problems, including posttraumatic stress disorder (PTSD) and depression. Recognizing that many gunshot injury survivors lack access to mental health care in the early aftermath of a shooting, there has been growing interest in the use of early, preventive mental health interventions to help prevent long-term mental health complications like PTSD as part of routine care for survivors in acute medical settings, where initial outreach to survivors may be more successful. This study evaluates clinical outcomes associated with one such early intervention-Skills for Psychological Recovery (SPR)-provided to gunshot injury survivors as part of a hospital-based early intervention program embedded in a Level 1 trauma center in the Midwestern United States. Clinic data from 100 survivors (74.0% male, 78.0% Black/African American) who received SPR were included in the present study. Results suggest that receiving SPR in the early aftermath of a shooting is associated with statistically significant reductions in both PTSD, F(1, 26.77) = 22.49, p < .001, and depression, F(1, 29.99) = 6.49, p = .016, symptoms. Outcomes did not vary as a function of either PTSD risk status or intervention delivery method (i.e., in-person, telehealth). These findings support the effectiveness and acceptability of SPR as an early intervention for gunshot injury survivors when delivered as part of a hospital-based early intervention program. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Promoting toddlers' self-regulation and healthy eating habits among families living in poverty: A randomized controlled trial of Recipe 4 Success.

The Recipe 4 Success preventive intervention targeted multiple factors critical to the health and well-being of toddlers living in poverty. This randomized controlled trial, which was embedded within Early Head Start home visits for 12 weeks, included 242 racially and ethnically diverse families (51% girls; toddler mean age = 2.58 years; data collected 2016-2019). Compared to parents in usual practice home visits, parents in Recipe 4 Success displayed greater sensitive scaffolding of toddlers' learning and more responsive food parenting practices (Cohen's d = .21-.30). Toddlers in Recipe 4 Success exhibited greater self-regulation and had healthier eating habits (Cohen's d = |.16-.35|). Results highlight the value of Recipe 4 Success in promoting parent and toddler behavior change that could have life-long benefits.

Impact of comorbidities on immediate post-operative complications in oral cavity free flap patients.

PURPOSE: To examine the relationship between comorbidities and the development of immediate post-operative complications in patients undergoing oral cavity composite resection (OCCR) with free flap (FF) reconstruction. MATERIALS AND METHODS: Retrospective analysis was completed on all consecutive OCCRs with FF reconstruction performed at a single quaternary care facility between 1999 and 2020. Comorbidities, immediate post-operative complications, patient demographics, and tumor characteristics were collected. Odds ratios (OR) with 95 % confidence intervals were calculated for associations between comorbidities and immediate post-operative complications. RESULTS: 320 patients who underwent OCCR with FF reconstruction were included. One hundred twenty-one (37.8 %) patients developed a post-operative complication during their initial hospital admission. The most common complications were non-pneumonia cardiopulmonary events (14.1 %), pneumonia (9.4 %), and wound infection (8.4 %). Other complications included flap compromise, bleeding, and fistula. On multivariate analysis, patients without comorbid conditions were less likely to develop a post-operative complication (OR 0.64; 0.41-0.98). Atrial fibrillation (OR 2.94; 1.17-7.39) and cerebrovascular disease (OR 2.28; 1.08-4.84) were associated with increased odds of developing any complications. Furthermore, cerebrovascular disease (OR: 2.33; 1.04-5.39) and peripheral vascular disease (OR: 2.7; 1.2-6.08) were independently associated with pneumonia. CONCLUSION: In this retrospective review of patients undergoing OCCR with FF reconstruction for oral cavity SCC, lack of identifiable comorbidities appeared to be protective for post-operative complications while atrial fibrillation and cerebrovascular disease were associated with increased odds of any complication. Pre-existing vascular disease was also associated with an increased risk of pneumonia.

Evolving approaches in paediatric thyroid cytopathology: A review.

The guidelines for the workup of thyroid nodules have been established in adult populations and secondarily applied to paediatric populations. In particular, The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is commonly applied to both adult and paediatric thyroid nodules. However, as paediatric nodules have distinct molecular drivers and behavioural trajectories, there is renewed interest in diagnostic and management strategies that are paediatric specific. Here, we review key differences between paediatric and adult thyroid cancer and recent literature evaluating the use of TBSRTC in paediatric populations.

Neonatal screening for spinal muscular atrophy: A pilot study in Brazil.

Spinal muscular atrophy (SMA) is considered one of the most common autosomal recessive disorders, with an estimated incidence of 1 in 10,000 live births. Testing for SMA has been recommended for inclusion in neonatal screening (NBS) panels since there are several therapies available and there is evidence of greater efficacy when introduced in the pre/early symptomatic phases. In Brazil, the National Neonatal Screening Program tests for six diseases, with a new law issued in 2021 stating that it should incorporate more diseases, including SMA. In the present study, dried blood spot (DBS) samples collected by the Reference Services of Neonatal Screening of RS and SP, to perform the conventional test were also screened for SMA, using real-time PCR, with SALSA MC002 technique. A total of 40,000 samples were analyzed, enabling the identification of four positive cases of SMA, that were confirmed by MLPA. Considering our sampling, Brazil seems to have an incidence comparable to the described in other regions. This work demonstrated that the use of the MC002 technique in samples routinely collected for the conventional NBS program is suitable to screen for SMA in our conditions and can be included in the expansion of the neonatal screening programs.

Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction.

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.

The USP46 complex deubiquitylates LRP6 to promote Wnt/ß-catenin signaling.

The relative abundance of Wnt receptors plays a crucial role in controlling Wnt signaling in tissue homeostasis and human disease. While the ubiquitin ligases that ubiquitylate Wnt receptors are well-characterized, the deubiquitylase that reverses these reactions remains unclear. Herein, we identify USP46, UAF1, and WDR20 (USP46 complex) as positive regulators of Wnt signaling in cultured human cells. We find that the USP46 complex is similarly required for Wnt signaling in Xenopus and zebrafish embryos. We demonstrate that Wnt signaling promotes the association between the USP46 complex and cell surface Wnt coreceptor, LRP6. Knockdown of USP46 decreases steady-state levels of LRP6 and increases the level of ubiquitylated LRP6. In contrast, overexpression of the USP46 complex blocks ubiquitylation of LRP6 by the ubiquitin ligases RNF43 and ZNFR3. Size exclusion chromatography studies suggest that the size of the USP46 cytoplasmic complex increases upon Wnt stimulation. Finally, we show that USP46 is essential for Wnt-dependent intestinal organoid viability, likely via its role in LRP6 receptor homeostasis. We propose a model in which the USP46 complex increases the steady-state level of cell surface LRP6 and facilitates the assembly of LRP6 into signalosomes via a pruning mechanism that removes sterically hindering ubiquitin chains.

Hashimoto's Thyroiditis and the Risk of Papillary Thyroid Cancer in Children.

The association between Hashimoto's thyroiditis (HT) and pediatric thyroid cancer is controversial. Most studies examining this connection have been based on adults, and larger studies in children are lacking. We performed a retrospective study of all sequential pediatric patients who underwent a thyroidectomy for a neoplasm at our institution over a twenty-year period in order to explore the link between HT and pediatric thyroid cancer. A total of 153 patients, median age 16.5 (interquartile range [IQR] 14.2-18.3) years, underwent thyroid surgery for a neoplasm. Patients were mainly female (80%) and White (84%). Median follow-up was 58.6 (IQR 20.7-105.4) months. Thirty-five (23%) patients had HT. Patients who underwent thyroid surgery and had HT were more likely to harbor a malignant neoplasm (p = 0.05); specifically, papillary thyroid carcinoma (PTC, p = 0.02). There was a difference in the distribution of HT among the subtypes of PTC (p = 0.03). Despite this, there was no difference in terms of survival between patients with/without HT. In conclusion, children with a thyroid malignancy, specifically, PTC, are more likely to have HT. The association between HT and pediatric PTC appears to be subtype-specific but does not seem to affect patient survival.

Fructose-containing food sources and blood pressure: A systematic review and meta-analysis of controlled feeding trials.

Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of the effect of different food sources of fructose-containing sugars at different levels of energy control on BP. We searched MEDLINE, Embase and the Cochrane Library through June 2021 for controlled trials ≥7-days. We prespecified 4 trial designs: substitution (energy matched substitution of sugars); addition (excess energy from sugars added); subtraction (excess energy from sugars subtracted); and ad libitum (energy from sugars freely replaced). Outcomes were systolic and diastolic BP. Independent reviewers extracted data. GRADE assessed the certainty of evidence. We included 93 reports (147 trial comparisons, N = 5,213) assessing 12 different food sources across 4 energy control levels in adults with and without hypertension or at risk for hypertension. Total fructose-containing sugars had no effect in substitution, subtraction, or ad libitum trials but decreased systolic and diastolic BP in addition trials (P<0.05). There was evidence of interaction/influence by food source: fruit and 100% fruit juice decreased and mixed sources (with sugar-sweetened beverages [SSBs]) increased BP in addition trials and the removal of SSBs (linear dose response gradient) and mixed sources (with SSBs) decreased BP in subtraction trials. The certainty of evidence was generally moderate. Food source and energy control appear to mediate the effect of fructose-containing sugars on BP. The evidence provides a good indication that fruit and 100% fruit juice at low doses (up to or less than the public health threshold of ~10% E) lead to small, but important reductions in BP, while the addition of excess energy of mixed sources (with SSBs) at high doses (up to 23%) leads to moderate increases and their removal or the removal of SSBs alone (up to ~20% E) leads to small, but important decreases in BP in adults with and without hypertension or at risk for hypertension. Trial registration: Clinicaltrials.gov: NCT02716870.

Association of Core Biopsy With Extranodal Extension in Surgically Treated Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

Importance: Extranodal extension (ENE) is an adverse feature in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and is an indication for adjuvant treatment escalation. Preoperative core needle biopsy (CNB) may cause lymph node capsule disruption related to ENE development; however, evidence regarding this association in OPSCC is lacking. Objective: To assess whether preoperative nodal CNB is associated with presence of ENE in final pathology findings among patients with HPV-associated OPSCC targeted for primary surgical resection. Design, Setting, and Participants: This retrospective cohort study was conducted at a single academic tertiary care center from 2012 to 2022. All patients with OPSCC treated with transoral robotic surgery were assessed for eligibility, and primary surgical patients with HPV-associated OPSCC and node-positive disease confirmed on neck dissection were included in analyses. Data were analyzed from November 28, 2022, to May 21, 2023. Exposure: Preoperative nodal CNB. Main Outcomes and Measures: The primary outcome was presence of ENE in final pathology findings. Secondary outcomes included adjuvant chemotherapy and recurrence rates. Outcomes of interest were investigated against patient demographic, clinical, and pathologic features. Results: Of 106 patients (mean [SD] age, 60.2 [10.9] years; 99 [93.4%] men) included in analyses, 23 patients (21.7%) underwent CNB. Mean (range) preoperative node size was 3.0 (0.9-6.0) cm. Pathologic node class was pN1 in 97 patients (91.5%) and pN2 in 9 patients (8.5%). A total of 49 patients (46.2%) had ENE identified in final pathology analysis. Of 94 patients who received adjuvant therapy, 58 (61.7%) underwent radiation therapy and 36 (38.3%) underwent chemoradiation therapy. There were 9 recurrences (8.5%). In univariate analysis, CNB was associated with ENE (odds ratio [OR], 2.70; 95% CI, 1.03-7.08), but there was no association in a multivariable model including pN class and preoperative node size (OR, 2.56; 95% CI, 0.97-7.27). Compared with pN1 class, pN2 class was associated with ENE (OR, 10.93; 95% CI, 1.32-90.80). There were no associations of ENE with preoperative node size, presence of cystic or necrotic nodes, fine needle aspiration, tobacco or alcohol exposure, pathologic T class, prior radiation, or age. Furthermore, use of CNB was not associated with macroscopic ENE, adjuvant chemotherapy, or recurrence. Conclusions and Relevance: This cohort study of patients with HPV-associated OPSCC found that preoperative nodal CNB was strongly associated with ENE in final pathology, supporting the possibility of an artifactual ENE component in this population.

A clindamycin acetylated derivative with reduced antibacterial activity inhibits articular hyperalgesia and edema by attenuating neutrophil recruitment, NF-κB activation and tumor necrosis factor-α production.

We recently demonstrated that clindamycin exhibits activities in acute and chronic models of pain and inflammation. In the present study, we investigated the effects of clindamycin and a clindamycin acetylated derivative (CAD) in models of acute joint inflammation and in a microbiological assay. Joint inflammation was induced in mice by intraarticular (i.a.) injection of zymosan or lipopolysaccharide (LPS). Clindamycin or CAD were administered via the intraperitoneal route 1 h before zymosan or LPS. Paw withdrawal threshold, joint diameter, histological changes, neutrophil recruitment, tumor necrosis factor-α (TNF-α) production and phosphorylation of the IκBα and NF-κB/p65 were evaluated. In vitro assays were used to measure the antibacterial activity of clindamycin and CAD and also their effects on zymosan-induced TNF-α production by RAW264.7 macrophages. Clindamycin exhibited activity against Staphylococcus aureus and Salmonella Typhimurium ATCC® strains at much lower concentrations than CAD. Intraarticular injection of zymosan or LPS induced articular hyperalgesia, edema and neutrophil infiltration in the joints. Zymosan also induced histological changes, NF-κB activation and TNF-α production. Responses induced by zymosan and LPS were inhibited by clindamycin (200 and 400 mg/kg) or CAD (436 mg/kg). Both clindamycin and CAD inhibited in vitro TNF-α production by macrophages. In summary, we provided additional insights of the clindamycin immunomodulatory effects, whose mechanism was associated with NF-κB inhibition and reduced TNF-α production. Such effects were extended to a clindamycin derivative with reduced antibacterial activity, indicating that clindamycin derivatives should be investigated as candidates to drugs that could be useful in the management of inflammatory and painful conditions.

Utilization of Instagram by Ophthalmology Residency Programs in the Era of COVID-19.

Purpose: The aim of this research is to describe the use of the social media platform, Instagram, by academic ophthalmology residency programs in the United States over time and consider the impact of the COVID-19 pandemic on ophthalmology's social media presence. Methods and Subjects: This cross-sectional study was conducted online by reviewing the publicly accessible Instagram accounts of all accredited US academic ophthalmology residency programs. Main Outcomes and Measures: Number of US ophthalmology residency programs with an affiliated Instagram account were analyzed by year of creation. The content of the top six accounts with the most followers was analyzed by evaluating amount of engagement within defined post categories. Results: Of the 124 ophthalmology residency programs, 78 (62.9%) were identified as having an affiliated Instagram account, 60 accounts (48.4%) were created during the years 2020 or 2021, and 62 (50.0%) accounts focused specifically on promoting the residency training program. Of the top six accounts with the most followers, post categories that received the most engagement were "Medical" and "Group Photo", while those that received the least engagement were "Department Bulletin" and "Miscellaneous." User engagement on posts as measured by likes and comments increased across multiple post categories after January 2020. Conclusion: Social media presence of ophthalmology residency programs on Instagram increased substantially in 2020 and 2021. As a result of the COVID-19 pandemic restricting in-person interactions, residency programs have used alternative platforms to reach applicants. Given the increasing use of such applications, social media will likely continue to become an important aspect of professional engagement in ophthalmology.

A case of novel mutation in ANOS1 (KAL1) gene and review of Kallmann syndrome.

Summary: Kallmann syndrome (KS) is a genetically heterogeneous condition characterized by hypogonadotropic hypogonadism with coexisting anosmia or hyposmia along with potential other phenotypic abnormalities depending on the specific genetic mutation involved. Several genetic mutations have been described to cause KS. The ANOS1 (KAL1) gene is responsible for 8% of mutations causing KS. A 17-year-old male presented to our clinic with delayed puberty and hyposmia, along with a family history suggestive of hypogonadism in his maternal uncle. Genetic testing for KS revealed complete exon 3 deletion in the ANOS1 gene. To the best of our knowledge, this specific mutation has not been previously described in the literature. Learning points: Missense and frameshift mutations in the KAL1 or ANOS1 gene located in the X chromosome are responsible for 8% of all known genetic mutations of Kallmann syndrome. Exon 3 deletion is one of the ANOS1 gene is a novel mutation, not reported before. Targeted gene sequencing for hypogonadotropic hypogonadism can be employed based on the phenotypic presentation.