Somatic variations in the meiosis-specific gene CrMER3 confer seedlessness in a citrus bud sport.

Seedlessness is a most valuable trait in fruit crops for fresh consumption and processing. The mutations in essential meiosis genes are known to confer sterility and seed abortion in plants. However, defects in meiosis have rarely been reported in fruit crops.

Polyploidization leads to salt stress resilience via ethylene signaling in citrus plants.

Polyploidization is a common occurrence in the evolutionary history of flowering plants, significantly contributing to their adaptability and diversity. However, the molecular mechanisms behind these adaptive advantages are not well understood. Through comprehensive phenotyping of diploid and tetraploid clones from Citrus and Poncirus genera, we discovered that genome doubling significantly enhances salt stress resilience.

[Expert consensus on the standardized application of whole exome sequencing technology in diagnosis of genetic disorders].

Next generation sequencing (NGS) technology is playing an increasingly important role in the diagnosis of genetic diseases. Whole exome sequencing (WES) which targets the coding regions of the genome has been widely used in the diagnosis of genetic diseases for its low cost and high efficiency. However, compared to conventional methods, the NGS process is intricate, and there is variability in the expertise of data analysts and variant interpreters, which may lead to inconsistencies in the outcomes.

PPAR affects hepatic lipid homeostasis by perturbing necroptosis signals in the intestinal epithelium.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPAR is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPAR signaling on cell death pathways is unknown.

Clinical utility of regions of homozygosity (ROH) identified in exome sequencing: when to pursue confirmatory uniparental disomy testing for imprinting disorders?

Objectives: Regions of homozygosity (ROH) could implicate uniparental disomy (UPD) on specific chromosomes associated with imprinting disorders. Though the algorithms for ROH detection in exome sequencing (ES) have been developed, optimal reporting thresholds and when to pursue confirmatory UPD testing for imprinting disorders remain in ambiguity. This study used a data-driven approach to assess optimal reporting thresholds of ROH in clinical practice.

CCNK Gene Deficiency Influences Neural Progenitor Cells Via Wnt5a Signaling in CCNK-Related Syndrome.

Objective: Rare variants of CCNK (cyclin K) give rise to a syndrome with intellectual disability. The purpose of this study was to describe the genotype-phenotype spectrum of CCNK-related syndrome and the underlying molecular mechanisms of pathogenesis.

Methods: We identified a number of de novo CCNK variants in unrelated patients.

A novel compound heterozygous mutation of the gene is associated with autosomal recessive osteopetrosis.

Osteopetrosis is a genetic condition of the skeleton characterized by increased bone density caused by osteoclast formation and function defects. Osteopetrosis is inherited in the form of autosomal dominant and autosomal recessive manner. We report autosomal recessive osteopetrosis (ARO; OMIM 611490) in a Chinese case with a history of scarce leukocytosis, vision and hearing loss, frequent seizures, and severe intellectual and motor disability.

A 25 Mainland Chinese cohort of patients with PURA-related neurodevelopmental disorders: clinical delineation and genotype-phenotype correlations.

PURA-related neurodevelopmental disorders (PURA-NDDs) include 5q31.3 microdeletion syndrome and PURA syndrome. PURA has been proposed as a candidate gene responsible for 5q31.

Improving variant prioritization in exome analysis by entropy-weighted ensemble of multiple tools.

Variant prioritization is a crucial step in the analysis of exome and genome sequencing. Multiple phenotype-driven tools have been developed to automate the variant prioritization process, but the efficacy of these tools in clinical setting with fuzzy phenotypic information and whether ensemble of these tools could outperform single algorithm remains to be assessed. A large rare disease cohort with heterogeneous phenotypic information, including a primary cohort of 1614 patients and a replication cohort of 1904 patients referred to exome sequencing, were recruited to assess the efficacy of variant prioritization and their ensemble.

Actin capping protein regulates postsynaptic spine development through CPI-motif interactions.

Dendritic spines are small actin-rich protrusions essential for the formation of functional circuits in the mammalian brain. During development, spines begin as dynamic filopodia-like protrusions that are then replaced by relatively stable spines containing an expanded head. Remodeling of the actin cytoskeleton plays a key role in the formation and modification of spine morphology, however many of the underlying regulatory mechanisms remain unclear.

Acetylome reprograming participates in the establishment of fruit metabolism during polyploidization in citrus.

Polyploidization leads to novel phenotypes and is a major force in evolution. However, the relationship between the evolution of new traits and variations in the post-translational modifications (PTM) of proteins during polyploidization has not been studied. Acetylation of lysine residues is a common protein PTM that plays a critical regulatory role in central metabolism.

A comparison of the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses.

Purpose: To compare the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses.

Methods: The clinical characteristics corresponding to pediatric urolithiasis patients that had undergone exome sequencing at our hospital between January 2016 and May 2021 were collected. Genetic analysis results were used to separate patients into positive and negative molecular diagnosis groups.

Changes in Homogalacturonan Metabolism in Banana Peel during Fruit Development and Ripening.

Though numerous studies have focused on the cell wall disassembly of bananas during the ripening process, the modification of homogalacturonan (HG) during fruit development remains exclusive. To better understand the role of HGs in controlling banana fruit growth and ripening, RNA-Seq, qPCR, immunofluorescence labeling, and biochemical methods were employed to reveal their dynamic changes in banana peels during these processes. Most HG-modifying genes in banana peels showed a decline in expression during fruit development.

Extended genetic analysis of exome sequencing for primary hyperoxaluria in pediatric urolithiasis patients with hyperoxaluria.

Purpose: Next generation sequencing-based exome sequencing can be used to identify genetic abnormalities in patients believed to be suffering from primary hyperoxaluria. We outline our efforts to improve the diagnostic capacity of exome sequencing for these patients.

Methods: We conducted a retrospective analysis of exome sequencing data from 77 pediatric urolithiasis patients with hyperoxaluria of unknown origin.

Transcriptomes and DNA methylomes in apomictic cells delineate nucellar embryogenesis initiation in citrus.

Citrus nucellar poly-embryony (NPE) is a mode of sporophytic apomixis that asexual embryos formed in the seed through adventitious embryogenesis from the somatic nucellar cells. NPE allows clonal propagation of rootstocks, but it impedes citrus cross breeding. To understand the cellular processes involved in NPE initiation, we profiled the transcriptomes and DNA methylomes in laser microdissection captured citrus apomictic cells.

An intronic variant disrupts mRNA splicing and causes -related skeletal dysplasia.

Objectives: Achondroplasia and hypochondroplasia are the most common forms of disproportionate short stature, of which the vast majority of cases can be attributed to the hotspot missense mutations in the gene . Here we presented cases with a novel cryptic splicing variant of gene and aimed to interrogate the variant pathogenicity.

Case Presentaiton: In whole exome sequencing of two patients with hypochondroplasia-like features, a intronic variant c.

Chromosomal microarray analysis in fetuses with high-risk prenatal indications: A retrospective study in China.

Objective: The present study aimed to determine the diagnostic value of prenatal chromosomal microarray analysis (CMA) for fetuses with several indications of being at high risk for various conditions.

Materials And Methods: This retrospective analysis included 1256 pregnancies that were prenatally evaluated due to high-risk indications using invasive CMA. The indications for invasive prenatal diagnosis mainly included ultrasound anomalies, high-risk for maternal serum screening (MSS), high-risk for non-invasive prenatal tests (NIPT), family history of genetic disorders or birth defects, and advanced maternal age (AMA).

Development and external validation of a COVID-19 mortality risk prediction algorithm: a multicentre retrospective cohort study.

Objective: This study aimed to develop and externally validate a COVID-19 mortality risk prediction algorithm.

Design: Retrospective cohort study.

Setting: Five designated tertiary hospitals for COVID-19 in Hubei province, China.

A 29 Mainland Chinese cohort of patients with Phelan-McDermid syndrome: genotype-phenotype correlations and the role of SHANK3 haploinsufficiency in the important phenotypes.

Background: Phelan-McDermid syndrome (PMS) or 22q13 deletion syndrome is a rare developmental disorder characterized by hypotonia, developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD) and dysmorphic features. Most cases are caused by 22q13 deletions encompassing many genes including SHANK3. Phenotype comparisons between patients with SHANK3 mutations (or deletions only disrupt SHANK3) and 22q13 deletions encompassing more than SHANK3 gene are lacking.

Diagnostic yield of additional exome sequencing after the detection of long continuous stretches of homozygosity (LCSH) in SNP arrays.

Long continuous stretches of homozygosity (LCSH) are associated with risk of recessive disorders. Though LCSH can be detected by SNP microarrays, additional testing is necessary to clarify the clinical significance. This study is to assess the yield of additional exome sequencing (ES) after LCSH detection and inform the likelihood of eventual diagnosis.

Integration of exome sequencing and metabolic evaluation for the diagnosis of children with urolithiasis.

Purpose: To investigate the prevalence of inherited causes in an early onset urolithiasis cohort and each metabolic subgroup.

Methods: A retrospective analysis of both metabolic and genomic data was performed for the first 105 pediatric urolithiasis patients who underwent exome sequencing at our hospital from February 2016 to October 2018. Measurements included the diagnostic yield of exome sequencing in the entire cohort and each metabolic subgroup (hyperoxaluria, hypocitraturia, hypercalciuria, hyperuricosuria and cystine stone subgroups).

RT-PCR analysis of mRNA revealed the splice-altering effect of rare intronic variants in monogenic disorders.

Background: Variants perturbing the normal splicing of pre-mRNA can lead to human diseases. The splice-altering effect and eventual consequence on gene function was sometimes uncertain and hinders a definitive molecular diagnosis.

Methods: The impact of four rare intronic variants on splicing was analyzed through reverse transcription - polymerase chain reaction (RT-PCR) analysis of mRNA derived from the peripheral blood of patients.