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Context
Precise genotype-phenotype correlations in Turner syndrome (TS) have not yet been deciphered. The chromosomal basis of the clinical TS-phenotype in the absence of X chromosome aberrations on the conventional karyotyping remains more and less unexplored.
Objective
To elucidate the high resolution chromosomal picture and analyze the genotype...
Contexts in source publication
Context 1
... 92.8% of patients with chromosome X CNVs simultaneously had CNVs detected on chromosome 14 also. Description of CNVs detected on chromosomes X and 14 are shown in Table 4. ...Citations
... The average of presentation in our study was 16.8 ±3.4 years and 93.75% of these patients were diagnosed after the age of 12 years. There was no significant 6 This age of presentation is quite late as compared to western population. In a follow-up study from Belgium in 2005, median age of presentation decreased from 11.2 years in 1991 to 6.6 years in 2003 with patients diagnosed at age >12 years decreased from 45% to 22%. ...
The present study was done to study the clinical profile and karyotype-phenotype corelation of turner syndrome patients in eastern UP, India.
The present study was a retrospective observational study conducted from January 2018 to December 2020 on newly diagnosed TS patients. All patients were screened for thyroid dysfunction, celiac disease, diabetes mellitus (DM), dyslipidaemia, liver dysfunction, hearing loss, cardiovascular anomalies and renal anomalies. Data was tabulated in Microsoft excel sheet and averages and means were calculated. Fischer exact test was used to assess the corelation of karyotype with clinical phenotypic features.
Total 16 patients were diagnosed with TS and 37.5% were classic 45 XO, 18.5% were mosaic 45X/46XX and rest 43.75% were of rarer TS variants. One patient had mosaicism for X chromosome with reciprocal autosomal translocation- 45X, t(12,20)(q24.1p13), 46X, t(12,20)(q24.1p13) *marker karyotype which is the first case reported so far. The average age of presentations was 16.8years ± 3.4years (range 8 to 23 years). One patient with karyotype 46,X, del(Xq22-28) had DM with negative anti-GAD antibodies and one patient with karyotype 46XX/46,X+marker had systemic lupus erythematosus (SLE). No significant karyotype and phenotype corelation was found in our study.
We report rare association of SLE with TS and a novel karyotype in TS involving mosaicism for X with autosomal translocation t(12,20). No significant karyotype-phenotype corelation was found in our study. More focused studies are needed to study the genes responsible for various manifestations in TS, pathogenic mechanisms of DM and SLE in TS and the effect of autosomal translocations in TS phenotype.
... In fact, there are studies reporting association of some of the polymorphisms studied, to pathological conditions [29][30][31]; one of these studies was conducted in Brazil and described the association of CNV gain of the 14q32.33 region with dental tumors [32], the reported copy gain in this 14q32.33 ...
Background
The human genome presents variation at distinct levels, copy number variants (CNVs) are DNA segments of variable lengths that range from several base pairs to megabases and are present at a variable number of copies in human genomes. Common CNVs have no apparent influence on the phenotype; however, some rare CNVs have been associated with phenotypic traits, depending on their size and gene content. CNVs are detected by microarrays of different densities and are generally visualized, and their frequencies analysed using the HapMap as default reference population. Nevertheless, this default reference is inadequate when the samples analysed are from people from Mexico, since population with a Hispanic genetic background are minimally represented. In this work, we describe the variation in the frequencies of four common CNVs in Mexican-Mestizo individuals.
Results
In a cohort of 147 unrelated Mexican-Mestizo individuals, we found that the common CNVs 2p11.2 (99.6%), 8p11.22 (54.5%), 14q32.33 (100%), and 15q11.2 (71.1%) appeared with unexpectedly high frequencies when contrasted with the HapMap reference (ChAS). Yet, while when comparing to an ethnically related reference population, these differences were significantly reduced or even disappeared.
Conclusion
The findings in this work contribute to (1) a better description of the CNVs characteristics of the Mexican Mestizo population and enhance the knowledge of genome variation in different ethnic groups. (2) emphasize the importance of contrasting CNVs identified in studied individuals against a reference group that—as best as possible—share the same ethnicity while keeping this relevant information in mind when conducting CNV studies at the population or clinical level.
... In a Turner syndrome population from India, it was found that more than 80% of the studied cases present polymorphisms in this locus, the authors concluded that the genes located in this locus and in 14q11.2 overlap with the network of genes associated with Turner Syndrome, suggesting that Turner and chromosome 14 syndromes have related pathways [25]; Ampli cation of the 14q32.2 and 20q11.22 ...
Background. The human genome presents variation at distinct levels, Copy number variants (CNV) are DNA segments of various lengths in bp that are present at a variable number of copies compared to a reference genome. CNV analysis has been done in almost all human populations and most of them have no apparent influence on the phenotype, yet some of them usually long sized, has been associated with pathologies. Recently however, the detection of common and benign CNV within different ethnic populations is becoming increasingly relevant as it helps in discerning real pathological variants and thus avoiding misinterpretations. The aim of this work is to describe four CNV frequently found in a cohort of 147 Mexican-Mestizo individuals.
Results: In this study we found four CNV 2p11.2, 8p11.22, 14q32.33 and 15q11.2, with a high frequency in the Mexican population when contrasted with the HapMap reference (ChAS), while when used an ethnically related population as a reference, the differences are reduced or disappear. The population studied does not show inbreeding or consanguinity.
Conclusion: CNV-type polymorphisms have frequencies that vary according to the ethnic group studied. It highlights the importance of analyzing the CNV of the studied individuals, with a reference group that -as far as possible- share the same ethnicity. These findings should be considered to avoid false associations of CNV with pathological conditions.
Turner syndrome affects 50 per 100,000 females, affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and US culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: 1) diagnosis and genetics, 2) growth, 3) puberty and estrogen treatment, 4) cardiovascular health, 5) transition, 6) fertility assessment, monitoring, and counselling, 7) health surveillance for comorbidities throughout the lifespan, and 8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.
Background:
Hepatocellular carcinoma (HCC) is a malignant disease with a poor prognosis. Among the treatment strategies for HCC, tumor immunotherapy (TIT) is a promising research hotspot, in which identifying novel immune-related biomarkers and selecting suitable patient population are urgent issues to be solved.
Methods:
In this study, an abnormal expression map of HCC cell genes was constructed using public high-throughput data from 7,384 samples (3,941 HCC vs. 3,443 non-HCC tissues). Through single-cell RNA sequencing (scRNA-seq) cell trajectory analysis, the genes defined as potential drivers of HCC cell differentiation and development were selected. By screening for both immune-related genes and those associated with high differentiation potential in HCC cell development, a series of target genes were identified. Coexpression analysis was performed using Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) to find the specific candidate genes involved in similar biological processes. Subsequently, nonnegative matrix factorization (NMF) was conducted to select patients suitable for HCC immunotherapy based on the coexpression network of candidate genes.
Results:
HSP90AA1, CDK4, HSPA8, HSPH1, and HSPA5 were identified as promising biomarkers for prognosis prediction and immunotherapy of HCC. Through the use of our molecular classification system, which was based on a function module containing 5 candidate genes, patients with specific characteristics were found to be suitable candidates for TIT.
Conclusions:
These findings provide new insights into the selection of candidate biomarkers and patient populations for future HCC immunotherapy.
Purpose of review:
Turner syndrome is the most common sex chromosome abnormality in female individuals, affecting 1/2000-1/2500 female newborns. Despite the high incidence of this condition, the mechanisms underlying the development of multiorgan dysfunction have not been elucidated.
Recent findings:
Clinical features involve multiple organ systems and include short stature, dysmorphic facial features, delayed puberty and gonadal failure, cardiac and renal abnormalities, audiologic abnormalities, and a high prevalence of endocrine and autoimmune disorders. Paucity of available genotype/phenotype correlation limits the ability of clinicians to provide accurate guidance and management. Given the advent of robust genetic testing and analysis platforms, developments in the genetic basis of disease are materializing at a rapid pace.
Summary:
The objective of this review is to highlight the recent advances in knowledge and to provide a framework with which to apply new data to the foundational understanding of the condition.
