Background: Skin cancers (SC) are complex diseases that develop from complex combinations of genetic and environmental risk factors. One of the most severe and rare genetic diseases predisposing to SC is the Xeroderma pigmentosum (XP) syndrome.
Objectives: First, to identify the genetic etiology of XP and to better classify affected patients. Second, to provide early molecular diagnosis for pre-symptomatic patient and finally to offer genetic counseling for related individuals.
Methods: Whole Exome Sequencing (WES) and Run Of Homozygosity (ROH) were performed for two patients belonging to two different multiplex consanguineous families. The identified mutations were confirmed by Sanger sequencing and researched in ten Tunisian families including a total of 25 affected individuals previously suspected as having XP group V (XP-V) form. All patients had mild dermatological manifestations, absence of neurological abnormalities and late onset of skin tumors.
Results: Screening for functional variations showed the presence of the ERCC2 p.Arg683Gln in XP14KA-2 patient and a novel mutation, DDB2 p. (Lys381Argfs*2), in XP51-MAH-1 patient. Sanger sequencing and familial segregation showed that the ERCC2 mutation is present at a homozygous state in 10 affected patients belonging to 3 families. The second mutation in DDB2, is present at a homozygous state in 5 affected cases belonging to the same family. These two mutations are absent in the remaining 10 affected patients. The ERCC2 c.2048G > A mutation is present in a medium ROH region (class B) suggesting that it mostly arises from ancient relatedness within individuals. However, the c.1138delG DDB2 mutation is present in a large ROH region (class C) suggesting that it arises from recent relatedness.
Conclusion: To our knowledge, this is the first study that identifies XP-D and XP-E complementation groups in Tunisia. These two groups are very rare and under-diagnosed in the world and were not reported in North Africa.
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http://dx.doi.org/10.1016/j.jdermsci.2017.10.015 | DOI Listing |
Medicine (Baltimore)
January 2025
Epilepsy Center, Children's Hospital Affiliated to Shandong University, Jinan, China.
Rationale: Developmental and epileptic encephalopathy (DEE) defines a group of severe and heterogeneous neurodevelopmental disorders. The voltage-gated potassium channel subfamily 2 voltage-gated potassium channel α subunit encoded by the KCNB1 gene is essential for neuronal excitability. Previous studies have shown that KCNB1 variants can cause DEE.
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January 2025
Laboratory for Innovative Drugs (Lab4IND), Computational Drug Design Center (HITMER), Bahçeşehir University, 34734 İstanbul, Türkiye.
is implicated in a range of conditions, including autism spectrum disorder, intellectual disability, seizures, autosomal recessive nonsyndromic intellectual disability, heterotaxy, and ciliary dysfunction. In order to understand the molecular mechanisms underlying these conditions, we focused on the structural and dynamic activity consequences of mutations within this gene. In this study, whole exome sequencing identified the c.
View Article and Find Full Text PDFHeliyon
January 2025
Faculty of Medicine, University of Surabaya, Surabaya, 60292, Indonesia.
Nasopharyngeal cancer (NPC), although rare in young individuals worldwide, is significantly influenced by the Epstein-Barr virus (EBV). Considering EBV's widespread prevalence, understanding its role in NPC's future occurrence, disease progression, clinical symptoms, metastatic tendencies, and prognosis is crucial. In this study, we extensively analyzed two young patients with NPC, who displayed distinct clinical features.
View Article and Find Full Text PDFJIMD Rep
January 2025
The Morris Kahn Laboratory of Human Genetics, Faculty of Health Sciences Ben Gurion University Beer-Sheva Israel.
The tightly-regulated spatial and temporal distribution of zinc ion concentrations within cellular compartments is controlled by two groups of Zn transporters: the 14-member ZIP/SLC39 family, facilitating Zn influx into the cytoplasm from the extracellular space or intracellular organelles; and the 10-member ZnT/SLC30 family, mobilizing Zn in the opposite direction. Genetic aberrations in most zinc transporters cause human syndromes. Notably, previous studies demonstrated osteopenia and male-specific cardiac death in mice lacking the ZnT5/ zinc transporter, and suggested association of two homozygous frameshift variants with perinatal mortality in humans, due to hydrops fetalis and hypertrophic cardiomyopathy.
View Article and Find Full Text PDFClin Pharmacol Ther
January 2025
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Pharmacogenetic testing can prevent severe toxicities from several oncology drug therapies; it also has the potential to improve the outcomes from supportive care drugs. Paired tumor and germline sequencing is increasingly common in oncology practice; these include sequencing of pharmacogenes, but the germline pharmacogenetic variants are rarely included in the clinical reports, despite many being clinically actionable. We established an informatics workflow to evaluate the clinical sequencing results for pharmacogenetic variants.
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