scholarly journals Clinical and Mutational Spectrum of Xeroderma Pigmentosum in Egypt: Identification of Six Novel Mutations and Implications for Ancestral Origins

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 295
Author(s):  
Eman Rabie ◽  
Khalda Amr ◽  
Suher Zada ◽  
Heba El-Sayed ◽  
Mohamad El Darouti ◽  
...  

Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. Skin and ocular symptoms are confined to sun exposed areas of the body. Patients have markedly increased risk for UV-induced skin, ocular, and oral cancers. Some patients develop neurodegenerative symptoms, including diminished tendon reflexes and microcephaly. In this study, we describe clinical and genetic findings of 36 XP patients from Egypt, a highly consanguineous population from North Africa. Thorough clinical evaluation followed by Sanger sequencing of XPA and XPC genes were done. Six novel and seven previously reported mutations were identified. Phenotype-genotype correlation was investigated. We report clinical and molecular findings consistent with previous reports of countries sharing common population structure, and geographical and historical backgrounds with implications on common ancestral origins and historical migration flows. Clinical and genetic profiling improves diagnosis, management, counselling, and implementation of future targeted therapies.

2021 ◽  
Vol 10 (8) ◽  
pp. 1552
Author(s):  
Guilaine Boursier ◽  
Cécile Rittore ◽  
Florian Milhavet ◽  
Laurence Cuisset ◽  
Isabelle Touitou

Mevalonate kinase-associated diseases (MKAD) are caused by pathogenic mutations in the mevalonate kinase gene (MVK) and encompass several phenotypically different rare and hereditary autoinflammatory conditions. The most serious is a recessive systemic metabolic disease called mevalonic aciduria, and the most recently recognized is disseminated superficial actinic porokeratosis, a dominant disease limited to the skin. To evaluate a possible correlation between genotypes and (1) the different MKAD clinical subtypes or (2) the occurrence of severe manifestations, data were reviewed for all patients with MVK variants described in the literature (N = 346), as well as those referred to our center (N = 51). The genotypes including p.(Val377Ile) (homozygous or compound heterozygous) were more frequent in mild systemic forms but were also sometimes encountered with severe disease. We confirmed that amyloidosis was more prevalent in patients compound heterozygous for p.(Ile268Thr) and p.(Val377Ile) than in others and revealed new associations. Patients homozygous for p.(Leu264Phe), p.(Ala334Thr) or compound heterozygous for p.(His20Pro) and p.(Ala334Thr) had increased risk of severe neurological or ocular symptoms. All patients homozygous for p.(Leu264Phe) had a cataract. The variants associated with porokeratosis were relatively specific and more frequently caused a frameshift than in patients with other clinical forms (26% vs. 6%). We provide practical recommendations focusing on phenotype–genotype correlation in MKAD that could be helpful for prophylactic management.


2020 ◽  
Vol 32 (1) ◽  
pp. 70
Author(s):  
Riezky Januar Pramitha ◽  
Sawitri Sawitri

Background: Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by photosensitivity, cutaneous pigmentary changes, and malignant tumor development at an early age. The basic defect underlying the clinical manifestations is nucleotide excision repair defect, leading to defective repair of ultraviolet (UV)-induced DNA. XP patients who are younger than 20 years of age have more than 1000-fold increased risk of developing malignant neoplasms of the skin, which commonly include squamous cell carcinoma, basal cell carcinoma, fibrosarcoma, and malignant melanoma. Malignant melanoma arises in only about 3% of XP patients. Purpose: To report a case of malignant melanoma in a child with XP. Case: A 7-years-old girl presented with multiple hypopigmentation and hyperpigmentation macules since age of two, throughout the body, more on sun-exposed areas. The physical examination showed solitary tumor extensive ulcero- proliferative surface with areas of hemorrhage and blackish pigmentation on the vertex region. Histological examination revealed a feature of nodular malignant melanoma, and the condition became worse after she underwent two cycles of chemotherapy. Discussion: Despite the rare occurrence, the nodular type of malignant melanoma in XP patients is the most aggressive and responsible for the fatal condition. Conclusion: Early detection of XP is necessary due to its fast-growing nature and high metastatic possibility as well as mortality index.


2020 ◽  
Vol 12 (2) ◽  
pp. 144-149
Author(s):  
Masazumi Onishi ◽  
Kanako Tsunoda ◽  
Fumihiko Maeda ◽  
Shinichi Moriwaki ◽  
Hiroo Amano

Xeroderma pigmentosum (XP) is an inherited autosomal recessive disorder characterized by photosensitivity and an increased risk of developing multiple skin neoplasms at sites exposed to the sun. We report a 73-year-old Japanese man with angiosarcoma of the auricle and an XP-variant, which is a very rare condition. In this case, long-term physical stimulation due to auricular deformation after surgery may have been the cause. Angiosarcoma associated with XP has a better prognosis than common angiosarcoma, perhaps because of the smaller tumor size. As XP patients are at high risk of skin neoplasms, they consult dermatologists regularly, and therefore skin tumors are likely to be detected early.


2013 ◽  
Vol 32 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Emina Čolak ◽  
Dragana Pap ◽  
Nada Majkić-Singh ◽  
Ivana Obradović

Summary Background: It has been reported that obesity is associated with metabolic syndrome, insulin resistance, cardiovascular risk but also with nonalcoholic fatty liver disease (NAFLD). The prevalence of obesity in children and adolescents is increasing rapidly all over the world. The aim of this study was to analyze the value of liver enzymes: AST, ALT and γGT in a group of obese students in order to establish their correlation to anthropometric parameters such as: BMI (body mass index), WC (waist circumference), HC (hip circumference), and WHR (waist-to-hip ratio) compared to non-obese students who comprised the control group (CG). Methods: In this study, 238 students from the University of Novi Sad of both sexes (126 men and 112 women) with a mean age of 22.32 ± 1.85 years were included. According to the body mass index (BMI) lower and higher than 25 kg/m2 and waist circumference (WC) lower and higher than 94 cm (80 cm for females) the whole group of 238 students was divided into 2 subgroups: the obese group at increased risk for CVD (Group 1) and the group at lower risk for CVD (Group 2). AST, ALT and γGT activities were determined in fasting blood samples. Results: Statistical processing data revealed significantly higher values of AST, ALT and γGT in the group of students with BMI>25 kg/m2, WC>94 cm for males and WC>80 cm for females, HC>108 cm for males and HC>111 cm for females, and WHR>0.90 for males and WHR>0.80 for females (P<0.001). Significant association was established between anthropometric parameters and liver enzyme levels (P<0.0001). Conclusions: Obese students with higher BMI, WC, HC and WHR values have higher liver enzyme activites and a higher chance to develop NAFLD in the future.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 735-735
Author(s):  
Charles Hoy-Ellis ◽  
Hyun Kim ◽  
Karen Fredriksen Goldsen

Abstract LGBTQ older adults are at significantly increased risk for poor mental and physical health, likely consequential to lifelong bias. Allostatic load (AL), the net effect of “wear and tear” on the body resulting from repeated, chronic over-activation of the psychophysiological stress response system. Utilizing the Health Equity Promotion Model, the aim of this study was to test potential life course predictors of AL, including interpersonal violence, legal marriage, and identity management in a sample of LGBTQ adults 50 to 97 years of age (n=317). Results from a series of hierarchical linear regression models showed that adult physical abuse and late identity disclosure for those who had been in an opposite-sex marriage predicted higher AL in this sample of LGBTQ older adults, indicating need for increased research on bias over the life course as contributory to AL and biopsychosocial dysfunction among LGBTQ older adults.


2020 ◽  
Vol 11 ◽  
pp. 215145932098036
Author(s):  
David W. Barton ◽  
C. Taylor Smith ◽  
Amit S. Piple ◽  
Sterling A. Moskal ◽  
Jonathan J. Carmouche

Introduction: Osteoporosis is often not clinically recognized until after a fracture occurs. Individuals who have 1 fracture are at increased risk of future fractures. Prompt initiation of osteoporosis treatment following fracture is critical to reducing the rate of future fractures. Antiresorptives are the most widely used class of medications for the prevention and treatment of osteoporosis. Many providers are hesitant to initiate antiresorptives in the acute post-fracture period. Concerns include interference with bone remodeling necessary for successful fracture healing, which would cause increased rates of non-union, malunion, and refracture. While such concerns should not extend to anabolic medications, physicians may also hesitate to initiate anabolic osteoporosis therapies due to high cost and/or lack of familiarity. This article aims to briefly review the available data and present a digestible narrative summary to familiarize practicing orthopaedic surgeons with the essential details of the published research on this topic. Results: The results of 20 clinical studies and key pre-clinical studies related to the effect of anti-resorptive medications for osteoporosis on fracture healing are summarized in the body of this narrative review. Discussion & Conclusions: While few level I studies have examined the impact of timing of initiation of osteoporosis medications in the acute post-fracture period, the few that have been published do not support these concerns. Specifically, data from level I clinical trials indicate that initiating bisphosphonates as early as 2 weeks post-fracture does not increase rates of non-union or malunion. By reviewing the available data, we hope to give clinicians the confidence to initiate osteoporosis treatment promptly post-fracture.


Author(s):  
Suzanne C. E. H. Sallevelt ◽  
Alexander P. A. Stegmann ◽  
Bart de Koning ◽  
Crool Velter ◽  
Anja Steyls ◽  
...  

Abstract Purpose Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% risk of affected offspring as a consequence. Until recently, comprehensive preconception carrier testing (PCT) for AR disorders was unavailable in routine diagnostics. Here we developed and implemented such a test in routine clinical care. Methods We performed exome sequencing (ES) for 100 consanguineous couples. For each couple, rare variants that could give rise to biallelic variants in offspring were selected. These variants were subsequently filtered against a gene panel consisting of ~2,000 genes associated with known AR disorders (OMIM-based). Remaining variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, after which only likely pathogenic and pathogenic (class IV/V) variants, present in both partners, were reported. Results In 28 of 100 tested consanguineous couples (28%), likely pathogenic and pathogenic variants not previously known in the couple or their family were reported conferring 25% risk of affected offspring. Conclusion ES-based PCT provides a powerful diagnostic tool to identify AR disease carrier status in consanguineous couples. Outcomes provided significant reproductive choices for a higher proportion of these couples than previous tests.


2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
S Singh ◽  
S Gupta ◽  
T S Mishra ◽  
B D Banerjee ◽  
T Sharma ◽  
...  

Abstract Introduction Nephrolithiasis is pathological calcification in the excretory passages of the body and is prevalent among 7.6% of Indians. We aimed to study the various risk factors associated with renal stones from India. Method It was a hospital-based case-control study conducted over 18 months in a tertiary hospital in Delhi. Cases were defined as patients with renal stones diagnosed on the basis of history and radiological examination. Controls were similar to cases in all respects except for the diagnosis and selected from the hospital. A total of 18 risk factors, including age, gender, heavy metals, stress, metabolic factors, alcohol intake, dietary habits, co-morbidities, etc. were assessed. Logistic regression analysis was performed to calculate the strength of the risk associations. Results In the analysis of 60 cases and controls, we found 6 times, 5.5 times, and 2.4 times increased odds of renal stones in patients with increased arsenic, cadmium, and lead concentrations in blood, respectively. Similarly, there are 3 times increased odds of renal stones in patients suffering from stress. Conclusions Exposure to smoke, occupation dust, and contaminated water may lead to an increased ingestion/inhalation of heavy metals like cadmium, arsenic, and predisposing people to an increased risk of renal stones.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1952.2-1952
Author(s):  
B. A. Esbensen ◽  
I. K. Roelsgaard ◽  
S. K. Larsen ◽  
T. Thomsen

Background:Smoking is one of the most significant modifiable exosomes risk factors for rheumatoid arthritis (RA) (1). Studies suggest that 25-30% of people with RA in Denmark smoke (2). This is almost twice as many as in the background population in Denmark. People with RA have a significant increased risk of severe comorbidity including cardiovascular disease. In addition, there are indications that smokers with RA have a poorer effect of the medical inflammatory treatment compared to non-smokers, and consequently more difficult to achieve remission of the disease activity (3). Tobacco addiction is complex and can be a challenge in smoking cessation. In addition to physiological dependence, habits and social and environmental factors may influence addiction. Tobacco smoking is associated with an addiction to nicotine and it is unexplored how this addiction appears in people with RA.Objectives:The aim of this study was to examine from the patient’s perspective how tobacco addiction appears in people with rheumatoid arthritis.Methods:We conducted a qualitative study based on a hermeneutics approach. People with RA who previously had participated in a randomized controlled study (4) about smoking cessation conducted at the Center for Rheumatology and Spine Diseases at Rigshospitalet, Denmark were recruited for semi-structured interviews.Results:In total, 12 people with RA (50% female) were included in the study. The median age was 62 years and median RA disease duration was 12 years. The degree of physical dependence measured by Fagerströms Test for Nicotine dependence (FTND) was on average: 4.9 (score: 0-10, 0=nonphysical dependence).Three categories of how tobacco addiction appeared emerged during the analysis: 1)It develops into ingrown habitsreferring to the fact that smoking already in adolescence contributes to the development of specific physical, mental and social smoking behavior. Not all individuals considered themselves addicted to nicotine as they did not necessarily connect the nicotine to the ingrown habits. 2)The body craves for nicotinereferring to nicotine proved calming, while a lacking or insufficient dose caused withdrawal symptoms. Furthermore, smoking became a habit where a craving for smoking occurred in certain situations. 3)Ambivalence – for and againstreferring to the physical dependence and smoking habits making a smoking cessation difficult. Dependency to nicotine and challenges to quit smoking led to a feeling of ambivalence and a lack of control.Conclusion:Tobacco addiction appeared as a physical dependence and a habit, which, during a smoking cessation, led to ambivalent feelings. Therefore, based on this study, there is still a need for health professionals to talk to patients about smoking. But also, a need to articulate the complexity of addiction in order to support for smoking cessations. Information should be strengthened in the clinical practice in relation to nicotine’s implication in tobacco addiction as well as the consequences of tobacco smoking for individuals with RA.References:[1]Scott DL, Wolfe F, Huizinga TW. Lancet. 2010 ###[2]Loppenthin K, Esbensen BA, Jennum P, Ostergaard M, Tolver A, Thomsen T, et al. Clin Rheumatol. 2015. ###[3]Roelsgaard IK, Ikdahl E, Rollefstad S, Wibetoe G, Esbensen BA, Kitas GD, et al. Rheumatology (Oxford). 2019. ###[4]Roelsgaard IK, Thomsen T, Ostergaard M, Christensen R, Hetland ML, Jacobsen S, et al. Trials. 2017;18(1):570.###Disclosure of Interests:None declared


Author(s):  
Matthew F Warren ◽  
Kimberly A Livingston

Abstract The risk of vitamin D insufficiency in humans is a global problem that requires improving ways to increase vitamin D intake. Supplements are a primary means for increasing vitamin D intake, but without a clear consensus on what constitutes vitamin D sufficiency, there is toxicity risk with taking supplements. Chickens have been used in many vitamin D-related research studies, especially studies involving vitamin D supplementation. Our state-of-the-art review evaluates vitamin D metabolism and how the different hydroxylated forms are synthesized. We provide an overview with how vitamin D is absorbed, transported, excreted, and what tissues in the body store vitamin D metabolites. We also discuss a number of studies involving vitamin D supplementation with broilers and laying hens. Vitamin D deficiency and toxicity are also described and how they can be caused. The vitamin D receptor (VDR) is important for vitamin D metabolism. However, there is much more that can be understood with VDR in chickens. Potential research aims involving vitamin D and chickens should explore VDR mechanisms which could lead to newer insights with VDR. Utilizing chickens in future research to help with elucidating vitamin D mechanisms has great potential to advance human nutrition. Finding ways to increase vitamin D intake will be necessary because the coronavirus 2019 disease (COVID-19) pandemic is leading to increased risk of vitamin D deficiency in many populations. Chickens can provide a dual purpose with addressing pandemic-caused vitamin D deficiency: 1) vitamin D supplementation gives chickens added value with possibly leading to vitamin D-enriched meat and egg products; and 2) chickens’ use in research provides data for translational research. Expanding vitamin D-related research in chickens to include more nutritional aims in vitamin D status has great implications with developing better strategies to improve human health.


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