The pivotal role of long non-coding RNAs as potential biomarkers and modulators of chemoresistance in ovarian cancer (OC)
AbstractOvarian cancer (OC) is a fatal gynecological disease that is often diagnosed at later stages due to its asymptomatic nature and the absence of efficient early-stage biomarkers. Previous studies have identified genes with abnormal expression in OC that couldn ’t be explained by methylation or mutation, indicating alternative mechanisms of gene regulation. Recent advances in human transcriptome studies have led to research on non-coding RNAs (ncRNAs) as regulators of cancer gene expression. Long non-coding RNAs (lncRNAs), a class of ncRNAs with a length greater than 200 nucleotides, have been identified as crucial ...
Source: Human Genetics - January 26, 2024 Category: Genetics & Stem Cells Source Type: research
Vitamin D-binding protein deficiency: an underrecognized Mendelian disorder of vitamin D metabolism
We present the case of a child with persistently low 25OH vitamin D levels despite replacement therapy. Exome sequencing revealed a novel homozygous nonsense variant in theGC gene, leading to undetectable levels of VDBP. Interestingly, exome sequencing also revealed a homozygous loss-of-function variant inZNF142, which likely explains the additional clinical features of recurrent febrile convulsions and global developmental delay. Our findings corroborate the two previously reported patients with autosomal recessive VDBP deficiency caused by biallelicGC variants and emphasize the importance of measuring VDBP levels in case...
Source: Human Genetics - January 24, 2024 Category: Genetics & Stem Cells Source Type: research
Expansion of the complex genotypic and phenotypic spectrum of FGFR2-associated neurocutaneous syndromes
We report on a girl with cutaneous nevi, ocular malformations, macrocephaly, mild developmental delay, and the initial clinical diagnosis of Schimmelpenning –Feuerstein–Mims syndrome, a very rare mosaic neurocutaneous disorder caused by postzygotic missense variants inHRAS,KRAS, andNRAS. Exome sequencing of blood and affected skin tissue identified the mosaic variant c.1647=/T > G p.(Asn549=/Lys) in FGFR2, upstream of the RAS signaling pathway. The variant is located in the tyrosine kinase domain of FGFR2 in a region that regulates the activity of the receptor and structural mapping and functional characteriza...
Source: Human Genetics - January 24, 2024 Category: Genetics & Stem Cells Source Type: research
Vitamin D-binding protein deficiency: an underrecognized Mendelian disorder of vitamin D metabolism
We present the case of a child with persistently low 25OH vitamin D levels despite replacement therapy. Exome sequencing revealed a novel homozygous nonsense variant in theGC gene, leading to undetectable levels of VDBP. Interestingly, exome sequencing also revealed a homozygous loss-of-function variant inZNF142, which likely explains the additional clinical features of recurrent febrile convulsions and global developmental delay. Our findings corroborate the two previously reported patients with autosomal recessive VDBP deficiency caused by biallelicGC variants and emphasize the importance of measuring VDBP levels in case...
Source: Human Genetics - January 24, 2024 Category: Genetics & Stem Cells Source Type: research
Expansion of the complex genotypic and phenotypic spectrum of FGFR2-associated neurocutaneous syndromes
We report on a girl with cutaneous nevi, ocular malformations, macrocephaly, mild developmental delay, and the initial clinical diagnosis of Schimmelpenning –Feuerstein–Mims syndrome, a very rare mosaic neurocutaneous disorder caused by postzygotic missense variants inHRAS,KRAS, andNRAS. Exome sequencing of blood and affected skin tissue identified the mosaic variant c.1647=/T > G p.(Asn549=/Lys) in FGFR2, upstream of the RAS signaling pathway. The variant is located in the tyrosine kinase domain of FGFR2 in a region that regulates the activity of the receptor and structural mapping and functional characteriza...
Source: Human Genetics - January 24, 2024 Category: Genetics & Stem Cells Source Type: research
Bi-allelic missense variants in MEI4 cause preimplantation embryonic arrest and female infertility
AbstractPreimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, andMei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date,MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygousMEI4 variants —namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Al...
Source: Human Genetics - January 22, 2024 Category: Genetics & Stem Cells Source Type: research
Exploring the effects of missense mutations on protein thermodynamics through structure-based approaches: findings from the CAGI6 challenges
AbstractMissense mutations are known contributors to diverse genetic disorders, due to their subtle, single amino acid changes imparted on the resultant protein. Because of this, understanding the impact of these mutations on protein stability and function is crucial for unravelling disease mechanisms and developing targeted therapies. The Critical Assessment of Genome Interpretation (CAGI) provides a valuable platform for benchmarking state-of-the-art computational methods in predicting the impact of disease-related mutations on protein thermodynamics. Here we report the performance of our comprehensive platform of struct...
Source: Human Genetics - January 16, 2024 Category: Genetics & Stem Cells Source Type: research
Genome-wide DNA methylation of lesional and peri-lesional skin in vitiligo: a comparative and integrated analysis of multi-omics in Chinese population
AbstractSeveral studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment. S...
Source: Human Genetics - January 6, 2024 Category: Genetics & Stem Cells Source Type: research
Genomic analysis of presumed perinatal stroke in Saudi Arabia reveals a strong monogenic contribution
This study suggests that monogenic disorders are important contributors to the pathogenesis of PPS and should be investigated by untargeted sequencing especially when traditional risk factors are excluded. (Source: Human Genetics)
Source: Human Genetics - January 5, 2024 Category: Genetics & Stem Cells Source Type: research
Genome-wide association and Mendelian randomization analysis provide insights into the shared genetic architecture between high-dimensional electrocardiographic features and ischemic heart disease
AbstractObservational studies have revealed that ischemic heart disease (IHD) has a unique manifestation on electrocardiographic (ECG). However, the genetic relationships between IHD and ECG remain unclear. We took 12-lead ECG as phenotypes to conduct genome-wide association studies (GWAS) for 41,960 samples from UK-Biobank (UKB). By leveraging large-scale GWAS summary of ECG and IHD (downloaded from FinnGen database), we performed LD score regression (LDSC), Mendelian randomization (MR), and polygenic risk score (PRS) regression to explore genetic relationships between IHD and ECG. Finally, we constructed an XGBoost model...
Source: Human Genetics - January 5, 2024 Category: Genetics & Stem Cells Source Type: research
Genomic analysis of presumed perinatal stroke in Saudi Arabia reveals a strong monogenic contribution
This study suggests that monogenic disorders are important contributors to the pathogenesis of PPS and should be investigated by untargeted sequencing especially when traditional risk factors are excluded. (Source: Human Genetics)
Source: Human Genetics - January 5, 2024 Category: Genetics & Stem Cells Source Type: research
