A Familial 4q12 Deletion Involving KIT Gene Causes Piebaldism

Piebaldism is a rare, autosomal dominant disorder characterized by the congenital absence of melanocytes in affected areas of the skin and hair. We report on a familial 4q12 deletion that involves the KIT gene and causes piebaldism in affected individuals. Wholegenome genotyping analysis of the proband using HumanCytoSNP- 12v2.1 BeadChips (Illumina Inc., San Diego, CA, USA, revealed a 1.34-Mb microduplication of 1q21.1q21.2 and a 2.7-Mb microdeletion of 4q12. The analysis of the parents confirmed the paternal origin of the 4q12 microdeletion. The clinical and molecular findings in the proband and his affected relatives showed that the 2.7-Mb 4q12 microdeletion, the smallest microdeletion reported to date, causes isolated piebaldism due to the loss of the KIT gen

A Familial 4q12 Deletion Involving KIT Gene Causes Piebaldism

T Piebaldism is a rare, autosomal dominant disorder characterized by the congenital absence of melanocytes in affected areas of the skin and hair. We report on a familial 4q12 deletion that involves the KIT gene and causes piebaldism in affected individuals. Wholegenome genotyping analysis of the proband using HumanCytoSNP12v2.1 BeadChips (Illumina Inc., San Diego, CA, USA, revealed a 1.34-Mb microduplication of 1q21.1q21.2 and a 2.7-Mb microdeletion of 4q12. The analysis of the parents confirmed the paternal origin of the 4q12 microdeletion. The clinical and molecular findings in the proband and his affected relatives showed that the 2.7-Mb 4q12 microdeletion, the smallest microdeletion reported to date, causes isolated piebaldism due to the loss of the KIT gene

Diagnostic Testing in Epilepsy Genetics Clinical Practice

Changing landscape of epilepsy genetic testing gives vast opportunities to both patients and clinicians. Significance of precise genetic diagnosis in patients affected by epilepsy cannot be overestimated: it not only gives the opportunities of personalized therapeutical approaches but is also associated with multiple additional benefits for patients, their families, and society. Although the burden of Mendelian and chromosomal diseases amenable to current diagnostic testing measures is unknown, recently, we have comprised a database of more than 880 human genes associated with monogenic diseases involving epilepsy or seizures, EpiGene database (http://www.kimg.eu/en/tools/epigene-database). Besides, more than 50 chromosomal syndromes are related to epilepsy or seizures. Currently, there are no recommendations or guidelines for genetic testing in epilepsy patients addressing specificities of next-generation sequencing technologies. However, as every genetic testing modality has its own characteristics of specificity/sensitivity, range of clinical indications, and possible bioethical and psychosocial implications, genetic testing in epilepsies must be properly selected and applied along with proper clinical genetics/genetic counseling services. In this chapter, an overview of genetic testing modalities and workflows taking into account genetic architecture of epilepsies is given, and practical aspects of genetic testing in epilepsies, including advantages/limitations and clinical utility of tests, are discussed

Dysregulation of microRNAs as the risk factor of lymph node metastasis in papillary thyroid carcinoma: systematic review

Papillary thyroid carcinoma (PTC) has an excellent prognosis with a relatively low mortality rate, but a small portion of PTC patients suffer from an aggressive form of the disease. In such cases early detection of lymph node metastasis (LNM) is as paramount as it is problematic. The routine use of central neck lymph node dissection is not recommended. New methods to detect LNM are needed. MicroRNAs are a potential biomarker for diagnosis and prognosis of PTC. In this review we summarise the current knowledge regarding dysregulated miRNAs and their association with LNM in PTS patients. The PubMed and EBSCO databases were searched using terms for “microRNA”, “thyroid carcinoma”, and “prognosis” by using Boolean operators. Based on eligibility and exclusion criteria, articles were screened and reviewed in full, methodological data of included studies were extracted, and risk of bias analysis performed. In total, 446 unique studies were extracted from the mentioned databases, and based on inclusion and exclusion criteria 27 studies were included in this review. Of them 17 analysed tissue microRNAs, 5 analysed circulating microRNAs, and 5 studies analysed both tissue and circulating samples. MiRNA-146B, miRNA-221, miRNA-222, miRNA-21, miRNA-204, miRNA-451, miRNA-199a-3p, and miRNA-30a-3p were dysregulated in at least 2 separate studies. A sizable portion of studies failed to show statistically significant differences in miRNA expression between LNM-positive and -negative patients. Different methodologies and disparities of patient populations could explain these discrepancies.\ This research supports the statement that specific up- and downregulated miRNAs are associated with LNM in PTC patients. However, the prognostic value of these miRNAs is limited. Additional targeted cohort studies are required to elucidate the role of miRNAs in defining individualised treatment strategies for thyroid cancer patients

X-linked juvenile retinoschisis: phenotypic and genetic characterization

Juvenile X-linked retinoschisis (XLRS, MIM#312700) belongs to a group of the vitreoretinal dystrophies. We aimed to describe the phenotype-genotype correlation of three XLRS cases in juveniles with different novel mutations from the Lithuanian population. The patients demonstrated macular retinoschisis and typical cyst-like cavities on spectral-domain optical coherence tomography (SD-OCT) images. The mean central foveal thickness was 569.7 µm. Two patients presented with peripheral retinoschisis. Flash electroretinogram demonstrated a reduced b/a ratio (T (p.R200L) mutation was detected in one case, showing to be pathogenic in silico analysis. c. (92_97) insC (p.W33fs) mutation was identified for another patient, indicating the variant is possibly damaging in silico analysis. The third case was identified with a pathogenic mutation c.422C>G (p.R141H), HGMD CM981753. These are the first cases of XLRS in the Lithuanian population confirmed by molecular genotyping. Presented patients had a different genotype but similar phenotypic traits

Association of hair glucocorticoid levels with sleep quality indicators: a pilot study in apparently healthy perimenopausal and menopausal women

BackgroundPoor sleep quality is associated with different physical and mental health diseases. It is proposed that increased hypothalamic-pituitary-adrenal axis activity is a potential contributor affecting sleep pattern and quality. We aimed to analyze the relationship between subjective sleep quality indicators and hair glucocorticoid levels among relatively healthy perimenopausal and postmenopausal women.MethodsA total of 145 women aged 50–64 y.o. were enrolled in the cross-sectional pilot study. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index, while stress level was measured using the Perceived Stress Scale. Hair cortisol and cortisone levels were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry.ResultsStatistically significant positive relationship was found between hair cortisol concentration and Pittsburgh sleep quality index score. Similarly, statistically significant positive associations were observed between hair total glucocorticoid level and Pittsburgh sleep quality index, sleep disturbance, and Perceived Stress Scale scores. Subjects with prolonged sleep latency had significantly higher hair cortisol and total hair glucocorticoid concentrations compared with individuals whose sleep latency is not disturbed. Additionally, Chi-squared test indicated that lower hair cortisol concentration was significantly related to better sleep efficiency.ConclusionIncreased hair glucocorticoid (cortisol, cortisone) levels were found to be related with worse sleep quality measured by Pittsburgh sleep quality index score

Association of BMP4 polymorphisms with non-syndromic cleft lip with or without cleft palate and isolated cleft palate in Latvian and Lithuanian populations

Cleft lip with or without cleft palate (CLP and CL, respectively) and isolated cleft palate (CP) represent one of the most common human birth defects, with a prevalence of approximately 1 in 300-2500 depending on the population. Formation of non-syndromic CL/CLP and CP arises from the interaction of environmental and genetic factors. The objective of this study was to investigate the association between the BMP4 gene (encoding bone morphogenetic protein 4) and non-syndromic CL/CLP and CP in order to clarify the role of this gene in the aetiology of the malformation in Latvian and Lithuanian populations. We genotyped three markers of the BMP4 gene (rs17563, rs2071047 and rs1957860) in order to perform single marker and haplotype association analyses for Latvian and Lithuanian non-syndromic CL/CLP and CP patients and controls. Transmission disequilibrium test was also conducted for Latvian and Lithuanian proband-parent trios. The case-control analysis revealed that SNP rs2071047 allele A was associated with a decreased risk of CL/CLP in the Latvian population, which was confirmed by the haplotype analysis. A modest association was detected between SNP rs1957860 and CP in the Lithuanian population, where allele C was associated with a decreased risk of this cleft phenotype, corroborating haplotype analysis data. Our findings support a role of the BMP4 gene in the aetiology of non-syndromic CL/CLP and CP in the studied populations.publishersversionPeer reviewe

Inhibitory capacity of Rhus coriaria L. extract and its major component methyl gallate on Streptococcus mutans biofilm formation by optical profilometry: Potential applications for oral health

Streptococcus mutans (S. mutans) bacterium is the most well recognized pathogen involved in pathogenesis of dental caries. Its virulence arises from its ability to produce a biofilm and acidogenicity, causing tooth decay. Discovery of natural products capable to inhibit biofilm formation is of high importance for developing health care products. To the best of our knowledge, in all previous scientific reports, a colorimetric assay was applied to test the effect of sumac and methyl gallate (MG) on S. mutans adherence. Quantitative assessment of the developed biofilm should be further performed by applying an optical profilometry assay, and by testing the effect on both surface roughness and thickness parameters of the biofilm. To the best of our knowledge, this is the first study to report the effect of sumac extract and its constituent MG on biofilm formation using an optical profilometry assay. Testing antibacterial activity of the sumac extract and its fractions revealed that MG is the most bioactive component against S. mutans bacteria. It reduced S. mutans biofilm biomass on the polystyrene surface by 68‑93%, whereas 1 mg/ml MG was able to decrease the biofilm roughness and thickness on the glass surface by 99%. MG also prevented a decrease in pH level by 97%. These bioactivities of MG occurred in a dose‑dependent manner and were significant vs. untreated bacteria. The findings are important for the development of novel pharmaceuticals and formulations of natural products and extracts that possess anti‑biofilm activities with primary applications for oral health, and in a broader context, for the treatment of various bacterial infections.The present study was supported by the Al‑Qasemi Research Foundation, the Ministry of Science, Technology and Space (Israel) and the Faculty of Medicine, Vilnius University (Lithuania)