International journal of molecular epidemiology and genetics最新文献

Nabais Sa-de Vries syndrome (NSDVS) is a neurodevelopmental disorder first described in 2020. The syndrome is caused by de novo missense mutations in speckle-type pox virus and zinc finger protein (SPOP) on chromosome 17q21. The syndrome is divided into two forms (NSDVS Type 1 and NSDVS Type 2) based on the consequence of the mutation involved. In this report, we present the clinical features in a young male patient with suspected NSDVS1 and summarize the features of the reported affected individuals thus far, with a focus on the ophthalmic manifestations. Similar to other individuals with NSDVS1, he had features of congenital microcephaly, developmental delay, behavioral abnormalities, hearing loss, and facial dysmorphisms. Ocular and periorbital manifestations in this patient included thick high-arched eyebrows, mild synophrys, long eyelashes, ptosis, and downslanting palpebral fissures; comparable to features described in other individuals with NSDVS1. In addition, this patient had esotropia that required multiple strabismus surgeries and a refractive error that required the use of corrective lenses. Although the consequences of specific mutations may result in a portion of the phenotypic differences between NSDVS1 and NSDVS2, the ophthalmic abnormalities between the two types may have significant overlap not explained by these bidirectional mutational effects.

Some blood group antigens are reported as a susceptibility marker for some diseases. For instance, HBGA (Histo-blood group antigen) which is controlled by gene FUT2 also considered as a susceptible marker. The FUT2 gene which exhibits the expression of alpha-1, 2-L-fucosyltransferase enzyme also leads to HBGA expression for the gut, and it provides a composition of the phenotypical profile that exists in some populations with unique histories of evolution and it can be considered as a marker of the genetic population. It is found to have an association with many diseases which is discussed in this review. Polymorphic mutations are known to inhibit and reduce its function which are population specific. Detailed understanding and deeper knowledge of its role in the pathogenesis and prevention of many diseases is required. FUT2 may also have a potential role in the case of COVID-19 as a susceptible marker due to its association with respiratory diseases and the ABO blood group. There is an utmost need for this kind of review knowing its importance and owing to limited collective information.

Genetics is responsible for 80% of androgenetic alopecia (AGA) predisposition. Several single nucleotide polymorphisms (SNPs) have been linked to AGA risk and the metabolism of its first-line therapies. Genotypic and allelic frequencies have not been described in Mexican individuals; therefore, the aim of this study was to describe the genetic distribution of SNPs associated with AGA predisposition and drug metabolism. Using Real Time-PCR, we genotyped SNPs rs4827528 (AR), rs7680591 (FGF5), rs1042028, rs1042157, rs788068 and rs6839 (SULT1A1) and rs776746 (CYP3A5) in 125 (controls = 60, cases = 65) male volunteers from Northern and Western Mexico. The SULT1A1 SNPs rs1042028 (C/T) and rs788068 (T/A/C) resulted in a 100% distribution of the ancestral allele C and mutated allele A, respectively; rs1042028 diverges from the previously reported frequency, while the rs788068 ancestral allele was found to be more predominant than the reported frequency. Rs1042028, rs788068 and rs4827528, were not in Hardy-Weinberg (HW) equilibrium; conversely, rs1042157 and rs6839, rs776746, and rs7680591 followed HW principles. A statistically significant difference (P<0.05) was obtained for the rs1042157 allelic frequency between cases and controls in Western Mexico. We reported the genotypic and allelic frequencies of seven polymorphisms in Mexican individuals from Northern and Western Mexico.

The NSUN2-intellectual disability syndrome is a rare disorder of the cellular transcriptome that prevents proper t-RNA splicing. This disorder interrupts cellular function and leads to an accumulation of RNA fragments, producing a constellation of symptoms including dysmorphic facies, hypotonia, microcephaly, and short stature. Eye manifestations have been reported but not well characterized. Our study presents a new case involving a 4-year-old boy with novel NSUN2 variants and clinical features consistent with the syndrome. In addition, through a systemic review, we discuss the 24 previously reported cases of the syndrome with an emphasis on the eye and ocular adnexa clinical features.

Dengue is an important vector borne viral infection. At present, it is endemic in many tropical countries. A molecular epidemiology of viral type in patients and mosquitoes can give useful epidemiology data for disease control. In Indochina, dengue is very common and the molecular epidemiology surveillance is continuously performed. Here, the authors reappraise on available local data from epidemiology studies of viral type in patients and mosquitoes in an endemic area of dengue in Indochina. According to analysis, the authors found that a considerable number of dengue patients do not have the same viral type with caught mosquito vector at their home. According to this study, a chance that a dengue patient gets pathogen from mosquito bite at home is 2.185%. The chance of getting dengue from the vector mosquito bite at home is not high. Hence, a public health policy to control of mosquito vector at home has to extend to universal control at any public places.

The outbreak of COVID-19 disease is an international public health concern. Therefore, the analysis of information related to mortality and disability due to COVID-19 is considered important, so the present study was designed and conducted with the aim of assessing COVID-19 Disability-Adjusted Life Years (DALYs) in Yazd. In Yazd province, all suspected cases of COVID-19 that would be referred to central hospitals in order to get confirmed through PCR or CT scan test, were recruited to our study. The fatality data of COVID-19 was gathered from the forensic medicine organization. The Disability-Adjusted Life Years (DALYs) combines in one measure years of life lost (YLL), the loss of healthy life due to premature mortality and years of life lived with disability (YLD), the loss of healthy life because of disease and disability. The total burden of COVID-19 was 23,472 years. The number of years lost due to premature death was 23385 and the number of years of life with disability due to COVID-19 was estimated to be 87 years. The disease burden was 12992 years for men and 10480 years for women. The overall incidence of COVID-19 was 1411 per 100,000, of which 1419 in men and 1402 in women per 100,000. The outbreak of COVID-19 pandemic affected a large population and the residents of Yazd Province lost many years of their lives due to this disease.

Introduction: Activating mutations in the BRAF gene have been reported in 0.8%-8% cases of NSCLC. Traditionally, diagnostics have mainly focused on detection of V600E and modalities like mutation specific IHC, allele specific real-time PCR have been utilized. This may underestimate true prevalence of the non-V600E variants. Broader panel NGS testing offers a one stop solution and may identify newer potentially targetable variants. This is a retrospective single center experience of patients with BRAF mutated NSCLC characterizing the molecular spectrum and clinicopathologic characteristics.

Methods: 260 patients underwent panel based NGS testing at our center, between 2017-2020. 13 BRAF mutant cases, were detected and were clinically reviewed.

Results: Thirteen cases of BRAF alterations were seen in out of 260 (5%) patients. Median age of the cohort was 62 years (range: 39-86 years) with a female predilection). Canonical BRAF V600E mutation was seen in 6 (46.2%) patients and 7 (53.8%) harbored a non-V600E alteration. Spectrum of non V600E alterations included G466E, G469A, N581I, V600_K601delins, D594G, L597Q, G649V and were commonly female (P>0.01) with a higher trend for liver metastases (P=0.09). Median PFS was 4.8 months on chemotherapy (P=0.8). All patients (13/13, 100%) were never smokers with an adenocarcinoma histology.

Conclusion: This is a single center experience from an Indian NSCLC cohort and shows higher prevalence of non-V600E than V600E mutation reported in literature. This may be attributed to increased use of NGS testing revealing otherwise missed alterations on sequential single gene testing.

Malignant melanoma is one of the most highly ranked cancers in terms of years of life lost. Hereditary melanoma with its increased familial susceptibility is thought to affect up to 12% of all melanoma patients. In the past, only a few high-penetrance genes associated with familial melanoma, such as CDKN2A and CDK4, have been clinically tested. However, findings now indicate that melanoma is a cancer most likely to develop not only due to high-penetrance variants but also due to polygenic inheritance patterns, leaving no clear division between the hereditary and sporadic development of malignant melanoma. Various pathogenic low-penetrance variants were recently discovered through genome-wide association studies, and are now translated into polygenic risk scores. These can show superior sensitivity rates for the prediction of melanoma susceptibility and related mixed cancer syndromes than risk scores based on phenotypic traits of the patients, with odds ratios of up to 5.7 for patients in risk groups. In addition to describing genetic findings, we also review the first results of epigenetic research showing constitutional methylation changes that alter the susceptibility to cutaneous melanoma and its risk factors.

Background: The occurrence of chromosomal diseases is a worldwide health problem. The use of agrochemicals, urbanization processes, and solar radiation can be predictive factors of the elevated risk of congenital malformations. In this sense, predicting the geographical potential of the distribution of chromosomal diseases has high relevance for public health.

Objectives: This study aimed to describe chromosomal prevalence in Brazil regions, from 2005 to 2015, to model a potential distribution of chromosomal disease occurrence probability associated with land use.

Methods: We used chromosomal prevalence to model a potential distribution of chromosomal diseases using machine learning algorithms. As the predictors of the models, we used the variables global forest canopy height, distance from the built-up area, and solar radiation. We characterized the predictive areas as potential occurrence of chromosomal diseases by land use and occupation.

Results: Georeferenced data of 43,672 karyotypes detected 7,237 cases of chromosomal diseases and used 5,362 to build the models. The models generated were accurate (TSS>0.5).

Discussion: The areas with greater occurrence of chromosomal diseases present a significant association with pasture areas, crops and agroforestry systems, and urbanized areas. This research is the first Brazilian study with this approach that seems promising in predicting the potential distribution of chromosomal diseases. Therefore, it can be an excellent management tool in public health.

Background: Hypertension has been continuing to be a major contributor to the global burden of disease and to the global mortality, leading to over 10 million deaths each year. The purpose of this study was to investigate the association between Adiponectin gene polymorphism with Essential hypertension (EH).

Methods: PubMed, EMbase, the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched independently by two investigators. Pooled odds ratios and 95% confidence intervals were calculated to estimate the associations of Adiponectin polymorphism with EH.

Results: Thirteen studies with 3198 cases and 3076 controls for meta-analysis (MA) were included in present study. Pooled results showed that rs2241766 polymorphism is associated with the risk of EH in the allelic model (G vs. T: OR=1.10; 95% CI, 1.01-1.21). In the <40 years subgroup, rs2241766 polymorphism is associated with the risk of EH in allele model (G vs. T: OR=1.43; 95% CI, 1.06-1.94), recessive model (GG vs. GT + TT: OR=5.26, 95% CI=1.47-18.76), homozygous model of GG (GG vs.TT: OR=5.27, 95% CI=1.47-18.95), and rs266729 in recessive model (GG vs. GT + TT: OR=2.33, 95% CI=1.33-4.08).

Conclusions: Our meta-analysis results show that the rs2241766 polymorphism is associated with the risk of hypertension. There still need a larger sample with better design to verify.