scholarly journals Xeroderma Pigmentosum: Clinical and Genetic Features and Therapeutic Approaches

2021 ◽  
Author(s):  
Tatyana S. Belysheva ◽  
Tatyana V. Nasedkina ◽  
Iryna S. Kletskaya ◽  
Anastasiya S. Volkova ◽  
Vera V. Semenova ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Xeroderma Pigmentosum ◽  
Malignant Tumors ◽  
Uv Light ◽  
Genetic Disorder ◽  
Sun Exposure ◽  
Therapeutic Approaches ◽  
Genetic Features ◽  
Oncological Diseases ◽  
Further Development

Xeroderma pigmentosum is rare genetic disorder characterized by increased skin sensitivity to damaging ultraviolet (UV) light. First symptoms manifest at early age in most cases (up to 75%). Chronic damage due to sun exposure is common, it has different stages of changes and risk of further development of malignant tumors that depends on the gene involved. Additionally to skin manifestations there are various neurological disorders such as progressive cognitive dysfunctions, sensorineural hearing loss, ataxia, pyramid and extrapyramidal disorders, areflexia. Treatment of patients with xeroderma pigmentosum is mostly symptomatic and preventive (protection against UV). Nowadays targeted medications for DNA repair and increasing cells resistance to UV light, thus preventing the oncological diseases, are under development.

scholarly journals Xeroderma pigmentosum and its dental implications

2015 ◽  
Vol 09 (01) ◽  
pp. 145-148 ◽  
Author(s):  
Hessa Al Wayli
Keyword(s):  
Uv Radiation ◽  
Xeroderma Pigmentosum ◽  
Genetic Disorder ◽  
Mouth Opening ◽  
Sun Exposure ◽  
The Body ◽  
Professional Management ◽  
Oral Pain ◽  
Carcinogenic Agents ◽  
Dental Professional

ABSTRACTXeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder characterized by defective DNA repair leading to clinical and cellular hypersensitivity to ultraviolet (UV) radiation and carcinogenic agents. Important clinical features are: Intense cutaneous photosensitivity, xerosis, poikiloderma, actinic keratosis, acute burning under minimal sun exposure, erythemas, hyperpigmented lentiginous macules, and malignant lesions in sun-exposed areas, including basocellular carcinoma, squamous cell carcinoma, and melanoma. There is a great involvement of many parts of the body, especially head and neck. Oral implications such as severe oral pain and mouth opening limitation were present due to perioral scars. The disorder is associated more commonly in populations where marriage of close blood relatives is common. Treatment of the disorder includes avoidance of UV radiation, topical application of 5-fluorouracil to treat actinic keratoses, and regular evaluation by an ophthalmologist, dermatologist, and neurologist. Genetic counseling is important aspects as an increased incidence of consanguineous marriages have been reported with this disorder. In addition, this paper discuss some important aspects concerning the role of the dental professional management of this entity, since XP patients require constant dental care and follow-up in order to control the occurrence of new lesions on the lips or inside oral cavity.

RECONSTRUCTION OF DNA-REPAIR DEFICIENT XERODERMA PIGMENTOSUM SKIN IN VITRO: A MODEL TO STUDY HYPERSENSITIVITY TO UV LIGHT

2004 ◽  
Author(s):  
Françoise Bernerd ◽  
Daniel Asselineau ◽  
Mathilde Frechet ◽  
Alain Sarasin ◽  
Thierry Magnaldo
Keyword(s):  
Dna Repair ◽  
Xeroderma Pigmentosum ◽  
Uv Light

scholarly journals Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 512
Author(s):  
Aleksandra Gilis-Januszewska ◽  
Anna Bogusławska ◽  
Kornelia Hasse-Lazar ◽  
Beata Jurecka-Lubieniecka ◽  
Barbara Jarząb ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Clinical Presentation ◽  
Age Of Onset ◽  
Malignant Tumors ◽  
Genetic Disorder ◽  
Family Members ◽  
Pancreatic Neuroendocrine Tumor ◽  
Index Patient ◽  
Generation Family

Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation.

scholarly journals Developmentally Regulated Oscillations in the Expression of UV Repair Genes in a Soilborne Plant Pathogen Dictate UV Repair Efficiency and Survival

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Shira Milo-Cochavi ◽  
Sheera Adar ◽  
Shay Covo
Keyword(s):  
Gene Expression ◽  
Fusarium Oxysporum ◽  
Plant Pathogen ◽  
Uv Light ◽  
Sun Exposure ◽  
The Sun ◽  
Repair Gene ◽  
Repair Capacity ◽  
Content Type ◽  
Repair Genes

ABSTRACT The ability to withstand UV damage shapes the ecology of microbes. While mechanisms of UV tolerance were extensively investigated in microorganisms regularly exposed to the sun, far less is known about UV repair of soilborne microorganisms. Fusarium oxysporum is a soilborne fungal plant pathogen that is resistant to UV light. We hypothesized that its UV repair capacity is induced to deal with irregular sun exposure. Unlike the SOS paradigm, our analysis revealed only sporadic increases and even decreases in UV repair gene expression following UVC irradiation or exposure to visible light. Strikingly, a major factor determining the expression of UV repair genes was the developmental status of the fungus. At the early stages of germination, the expression of photolyase increased while the expression of UV endonuclease decreased, and then the trend was reversed. These gene expression oscillations were dependent on cell cycle progression. Consequently, the contribution of photoreactivation to UV repair and survival was stronger at the beginning of germination than later when a filament was established. F. oxysporum germinates following cues from the host. Early on in germination, it is most vulnerable to UV; when the filament is established, the pathogen is protected from the sun because it is already within the host tissue. IMPORTANCE Fusarium oxysporum infects plants through the roots and therefore is not exposed to the sun regularly. However, the ability to survive sun exposure expands the distribution of the population. UV from the sun is toxic and mutagenic, and to survive sun exposure, fungi encode several DNA repair mechanisms. We found that Fusarium oxysporum has a gene expression program that activates photolyase at the first hours of germination when the pathogen is not established in the plant tissue. Later on, the expression of photolyase decreases, and the expression of a light-independent UV repair mechanism increases. We suggest a novel point of view to a very fundamental question of how soilborne microorganisms defend themselves against sudden UV exposure.

scholarly journals Photoprotection and Skin Pigmentation: Melanin-Related Molecules and Some Other New Agents Obtained from Natural Sources

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1537 ◽  
Author(s):  
Francisco Solano
Keyword(s):  
Human Skin ◽  
Uv Light ◽  
Stratospheric Ozone ◽  
Skin Pigmentation ◽  
Antioxidant Properties ◽  
Sun Exposure ◽  
Marine Organisms ◽  
Electromagnetic Spectrum ◽  
Chemical Structures ◽  
Skin Lightening

Direct sun exposure is one of the most aggressive factors for human skin. Sun radiation contains a range of the electromagnetic spectrum including UV light. In addition to the stratospheric ozone layer filtering the most harmful UVC, human skin contains a photoprotective pigment called melanin to protect from UVB, UVA, and blue visible light. This pigment is a redox UV-absorbing agent and functions as a shield to prevent direct UV action on the DNA of epidermal cells. In addition, melanin indirectly scavenges reactive oxygenated species (ROS) formed during the UV-inducing oxidative stress on the skin. The amounts of melanin in the skin depend on the phototype. In most phenotypes, endogenous melanin is not enough for full protection, especially in the summertime. Thus, photoprotective molecules should be added to commercial sunscreens. These molecules should show UV-absorbing capacity to complement the intrinsic photoprotection of the cutaneous natural pigment. This review deals with (a) the use of exogenous melanin or melanin-related compounds to mimic endogenous melanin and (b) the use of a number of natural compounds from plants and marine organisms that can act as UV filters and ROS scavengers. These agents have antioxidant properties, but this feature usually is associated to skin-lightening action. In contrast, good photoprotectors would be able to enhance natural cutaneous pigmentation. This review examines flavonoids, one of the main groups of these agents, as well as new promising compounds with other chemical structures recently obtained from marine organisms.

scholarly journals Familial adult myoclonic epilepsy (FAME): clinical features, molecular characteristics, pathophysiological aspects and diagnostic work-up

2021 ◽  
Vol 33 (4) ◽  
pp. 311-318
Author(s):  
Lorenz Peters ◽  
Christel Depienne ◽  
Stephan Klebe
Keyword(s):  
Clinical Features ◽  
Neurological Disorders ◽  
Genetic Disorder ◽  
Repeat Expansion ◽  
Myoclonic Epilepsy ◽  
Molecular Characteristics ◽  
Autosomal Dominant Disorder ◽  
Repeat Expansions ◽  
Diagnostic Work ◽  
Work Up

Abstract Familial adult myoclonic epilepsy (FAME) is a rare autosomal dominant disorder characterized by myoclonus and seizures. The genetic variant underlying FAME is an intronic repeat expansion composed of two different pentamers: an expanded TTTTA, which is the motif originally present at the locus, and an insertion of TTTCA repeats, which is usually located at the 3′ end and likely corresponds to the pathogenic part of the expansion. This repeat expansion has been identified so far in six genes located on different chromosomes, which remarkably encode proteins with distinct cellular localizations and functions. Although the exact pathophysiological mechanisms remain to be clarified, it is likely that FAME repeat expansions lead to disease independently of the gene where they occur. We herein review the clinical and molecular characteristics of this singular genetic disorder, which interestingly shares clinical features with other more common neurological disorders whose etiology remains mainly unsolved.

Neuroinflammation in Huntington’s disease: A starring role for astrocyte and microglia

2021 ◽  
Vol 19 ◽  
Author(s):  
Julieta Saba ◽  
Federico López Couselo ◽  
Julieta Bruno ◽  
Lila Carniglia ◽  
Daniela Durand ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Genetic Disorder ◽  
Cag Repeat ◽  
Inflammatory Factors ◽  
Therapeutic Approaches ◽  
Reactive Microglia ◽  
New Treatments ◽  
The Brain

: Huntington’s disease (HD) is a neurodegenerative genetic disorder caused by a CAG repeat expansion in the huntingtin gene. HD causes motor, cognitive, and behavioral dysfunction. Since no existing treatment affects the course of this disease, new treatments are needed. Inflammation is frequently observed in HD patients before symptom onset. Neuroinflammation, characterized by the presence of reactive microglia and astrocytes and inflammatory factors within the brain, is also detected early. However, in comparison with other neurodegenerative diseases, the role of neuroinflammation in HD is much less known. Work has been dedicated to altered microglial and astrocytic functions in the context of HD, but less attention has been given to glial participation in neuroinflammation. This review describes evidence of inflammation in HD patients and animal models. It also discusses recent knowledge on neuroinflammation in HD, highlighting astrocyte and microglia involvement in the disease and considering anti-inflammatory therapeutic approaches.

scholarly journals Xeroderma Pigmentosum: Ocular Findings in an Isolated Brazilian Group with an Identified Genetic Cluster

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Maria Claudia Schelini ◽  
Luis Fernando O. B. Chaves ◽  
Marcia C. Toledo ◽  
Francisco W. Rodrigues ◽  
Tauan de Oliveira ◽  
...  
Keyword(s):  
Ocular Surface ◽  
Xeroderma Pigmentosum ◽  
Genetic Disorder ◽  
Skin Pigmentation ◽  
Previous History ◽  
Case Series ◽  
Corneal Neovascularization ◽  
University Hospital ◽  
Ocular Symptoms ◽  
History Of

Purpose. Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder characterized by increased susceptibility to UV radiation- (UVR-) induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Eight different genes are affected, and the prevalence of the disease differs across the world. The present study describes the main ophthalmologic features and symptoms in patients with XP in this case series. Methods. Patients were examined consecutively at the University Hospital of the Federal University of Goias between January 2016 and June 2018. All patients underwent ophthalmologic examination and were asked about their ophthalmological history and the presence of ocular symptoms. Results. Twenty-one patients with genetic confirmation were evaluated. The genetic variants XPV and XPC were detected in the patients. The most prevalent findings include eyelid changes, observed in 80.9% of the patients, and ocular surface changes as punctate keratopathy, occurring in 16 patients (76.2%), corneal neovascularization, and corneal opacities. Six patients (28.5%) presented corneoconjunctival tumor. More than half of patients had previous history of treatment of ocular neoplasia. Ocular burning was the most reported symptom. Conclusions. The ocular characteristics identified in this study corroborate the existing literature, mainly related to the surface. Concerning the XP variant and the gravity of ocular signs, XPC has earlier and more severe symptoms than XPV. Due to their relative rarity, publications of XP cases are important to understand the possible damages caused by the disease in the eyes and surrounding area.

scholarly journals Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2746
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cell ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Therapeutic Strategy ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Effective Therapeutic Strategy ◽  
Cancer Types ◽  
The Brain

The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling pathways, such as aldehyde dehydrogenase (ALDH), CD133, epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin signaling, and Notch signaling, contribute to the initiation and progression of various liver cancer types. Importantly, CSCs are markedly resistant to conventional therapeutic approaches and current targeted therapeutics. Therefore, it is believed that selectively targeting specific markers and/or signaling pathways of hepatic CSCs is an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. Here, we provide an overview of the current knowledge on the hepatic CSC hypothesis and discuss the specific surface markers and critical signaling pathways involved in the development and maintenance of hepatic CSC subpopulations.

Sign in / Sign up

Export Citation Format

Share Document