Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies.

The killer-cell immunoglobulin-like receptor (KIR) gene complex, a highly polymorphic region of the human genome that encodes proteins involved in immune responses, poses strong challenges in genotyping owing to its remarkable genetic diversity and structural intricacy. Accurate analysis of KIR alleles, including their structural variations, is crucial for understanding their roles in various immune responses. Leveraging the high-quality genome assemblies from the Human Pangenome Reference Consortium (HPRC), we present a novel bioinformatic tool, the structural KIR annoTator (SKIRT), to investigate gene diversity and facilitate precise KIR allele analysis.

Implementing next-generation sequencing for diagnosis and management of hereditary hearing impairment: a comprehensive review.

Introduction: Sensorineural hearing impairment (SNHI), a common childhood disorder with heterogeneous genetic causes, can lead to delayed language development and psychosocial problems. Next-generation sequencing (NGS) offers high-throughput screening and high-sensitivity detection of genetic etiologies of SNHI, enabling clinicians to make informed medical decisions, provide tailored treatments, and improve prognostic outcomes.

Areas Covered: This review covers the diverse etiologies of HHI and the utility of different NGS modalities (targeted sequencing and whole exome/genome sequencing), and includes HHI-related studies on newborn screening, genetic counseling, prognostic prediction, and personalized treatment.

Relationship between genotype, phenotype, and refractive status in patients of inherited retinal degeneration.

Background: To elucidate the relationship between inherited retinal disease, visual acuity and refractive error development in Asian patients.

Subjects: Five hundred phakic eyes with refractive data were analysed in this retrospective cohort. Diseases were categorized by clinical phenotypes, and the prevalent genotypes identified in the Taiwan Inherited Retinal Degeneration Project were analysed.

Transcriptome Analysis of Mesenchymal Progenitor Cells Revealed Molecular Insights into Metabolic Dysfunction and Inflammation in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a female endocrine disorder with metabolic issues. Hyperandrogenism combined with hyperinsulinemia exacerbates the reproductive, metabolic, and inflammatory problems in PCOS patients. The etiology of PCOS is unclear.

Unsupervised clustering identified clinically relevant metabolic syndrome endotypes in UK and Taiwan Biobanks.

Metabolic syndrome (MetS) is a collection of cardiovascular risk factors; however, the high prevalence and heterogeneity impede effective clinical management. We conducted unsupervised clustering on individuals from UK Biobank to reveal endotypes. Five MetS subgroups were identified: Cluster 1 (C1): non-descriptive, Cluster 2 (C2): hypertensive, Cluster 3 (C3): obese, Cluster 4 (C4): lipodystrophy-like, and Cluster 5 (C5): hyperglycemic.

High prevalence of exon-13 variants in USH2A-related retinal dystrophies in Taiwanese population.

Background: Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype-phenotype correlations of USH2A-related retinal dystrophies in Taiwan.

Results: In our cohort, the mean age at first visit was 47.

Machine learning-based longitudinal prediction for GJB2-related sensorineural hearing loss.

Background: Recessive GJB2 variants, the most common genetic cause of hearing loss, may contribute to progressive sensorineural hearing loss (SNHL). The aim of this study is to build a realistic predictive model for GJB2-related SNHL using machine learning to enable personalized medical planning for timely intervention.

Method: Patients with SNHL with confirmed biallelic GJB2 variants in a nationwide cohort between 2005 and 2022 were included.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

Background: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response.

Methods: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT.

Metabolomics facilitates differential diagnosis in common inherited retinal degenerations by exploring their profiles of serum metabolites.

The diagnosis of inherited retinal degeneration (IRD) is challenging owing to its phenotypic and genotypic complexity. Clinical information is important before a genetic diagnosis is made. Metabolomics studies the entire picture of bioproducts, which are determined using genetic codes and biological reactions.

A novel framework for human leukocyte antigen (HLA) genotyping using probe capture-based targeted next-generation sequencing and computational analysis.

Human leukocyte antigen (HLA) genes play pivotal roles in numerous immunological applications. Given the immense number of polymorphisms, achieving accurate high-throughput HLA typing remains challenging. This study aimed to harness the human pan-genome reference consortium (HPRC) resources as a potential benchmark for HLA reference materials.

Complete genomic profiles of 1496 Taiwanese reveal curated medical insights.

Introduction: The population of Taiwan has a long history of ethno-cultural evolution. The Taiwanese population was isolated from other large populations such as the European, Han Chinese, and Japanese population. The Taiwan Biobank (TWB) project has built a nationwide database, particularly for personal whole-genome sequence (WGS) to facilitate basic and clinical collaboration nationally and internationally, making it one of the most valuable public datasets of the East Asian population.

Simulation-predicted and -explained inheritance model of pathogenicity confirmed by transgenic mice models.

Variants in the gap junction beta-2 () gene are the most common cause of hereditary hearing impairment. However, how variants lead to local physicochemical and structural changes in the hexameric ion channels of connexin 26 (Cx26), resulting in hearing impairment, remains elusive. In this study, using molecular dynamics (MD) simulations, we showed that detached inner-wall N-terminal "plugs" aggregated to reduce the channel ion flow in a highly prevalent V37I variant in humans.

Genotype-phenotype correlation in Taiwanese children with diazoxide-unresponsive congenital hyperinsulinism.

Objective: Congenital hyperinsulinism (CHI) is a group of clinically and genetically heterogeneous disorders characterized by dysregulated insulin secretion. The aim of the study was to elucidate genetic etiologies of Taiwanese children with the most severe diazoxide-unresponsive CHI and analyze their genotype-phenotype correlations.

Methods: We combined Sanger with whole exome sequencing (WES) to analyze CHI-related genes.

Clinical characteristics of neutropenic patients under antithyroid drug: Twelve-year experience in a medical center.

Background: Thionamide-induced agranulocytosis (TiA) is a rare adverse event with a reported incidence of approximately 0.1% to 1.75%.

L1cam alternative shorter transcripts encoding the extracellular domains were overexpressed in the intestine of L1cam knockdown mice.

Hirschsprung disease (HSCR) is a congenital disorder of functional bowel obstruction due to the absence of enteric ganglia in distal bowel. Different L1cam variants were reportedly associated with L1cam syndrome and HSCR, whose phenotypes lacked predictable relevance to their genotypes. Using next-generation sequencing (NGS), we found an L1CAM de novo frameshift mutation in a female with mild hydrocephalus and skip-type HSCR.

Revisiting Genetic Epidemiology with a Refined Targeted Gene Panel for Hereditary Hearing Impairment in the Taiwanese Population.

Hearing impairment is one of the most common sensory disorders in children, and targeted next-generation sequencing (NGS)-based genetic examinations can assist in its prognostication and management. In 2020, we developed a simplified 30-gene NGS panel from the original 214-gene NGS version based on Taiwanese genetic epidemiology data to increase the accessibility of NGS-based examinations. In this study, we evaluated the diagnostic performance of the 30-gene NGS panel and compared it with that of the original 214-gene NGS panel in patient subgroups with different clinical features.

Combining Panel-Based Next-Generation Sequencing and Exome Sequencing for Genetic Liver Diseases.

Objectives: To determine how advanced genetic analysis methods may help in clinical diagnosis.

Study Design: We report a combined genetic diagnosis approach for patients with clinical suspicion of genetic liver diseases in a tertiary referral center, using tools either tier 1: Sanger sequencing on SLC2SA13, ATP8B1, ABCB11, ABCB4, and JAG1 genes, tier 2: panel-based next generation sequencing (NGS), or tier 3: whole-exome sequencing (WES) analysis.

Results: In a total of 374 patients undergoing genetic analysis, 175 patients received tier 1 Sanger sequencing based on phenotypic suspicion, and pathogenic variants were identified in 38 patients (21.