Genetic Variants Supporting the Diagnosis of Primary Ciliary Dyskinesia in Japan.

Primary ciliary dyskinesia (PCD; OMIM 244400) is a rare genetic disorder affecting motile cilia and is characterized by impaired mucociliary clearance in the airway epithelium that leads to chronic oto-sinopulmonary manifestations. To date, over 50 PCD-causing genes have been identified, with these genes and their variants varying globally across populations. We performed targeted resequencing of 42 PCD-causative genes in 150 Japanese patients suspected of having PCD and identified pathogenic or likely pathogenic variants in 51 patients.

Transcriptional regulators and modulate inflammatory response genes in -infected human macrophages.

Unlabelled: Understanding the functions of human transcriptional regulatory genes and during infection is crucial; in a mouse model, homologous genes and have been shown to negatively regulate inflammatory response genes, including the type I interferon (IFN) response. The reduction of these genes in mice is associated with susceptibility to infection and the development of necrotizing granulomatous lesions. To investigate the involvement of and in human inflammatory response, we analyzed their regulatory manner in THP-1 macrophages infected with .

Primary Ciliary Dyskinesia Due to Compound Heterozygous Variants in CFAP221 with Obstructive Azoospermia: Young's Syndrome May Be a Phenotype of Primary Ciliary Dyskinesia.

We report the case of a 42-year-old man with bronchiectasis who had a history of infertility treatment for obstructive azoospermia. Young's syndrome was suspected based on the triad of obstructive azoospermia, sinusitis, and bronchiectasis. He had normal electron microscopy findings, normal nasal nitric oxide levels (116 nL/min), and no situs inversus.

Primary Ciliary Dyskinesia Caused by Homozygous DNAAF1 Mutations Resulting from a Consanguineous Marriage: A Case Report from Japan.

We present the case of a 58-year-old female patient with primary ciliary dyskinesia (PCD). She was born to parents with a consanguineous marriage. Chest computed tomography conducted at age 41 years indicated no situs inversus, and findings of bronchiectasis were limited to the middle and lingular lobes.

Impact of primary ciliary dyskinesia: Beyond sinobronchial syndrome in Japan.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by impaired motile cilia function, particularly in the upper and lower airways. To date, more than 50 causative genes related to the movement, development, and maintenance of cilia have been identified. PCD mostly follows an autosomal recessive inheritance pattern, in which PCD symptoms manifest only in the presence of pathogenic variants in both alleles.

FOXJ1 Variants Causing Primary Ciliary Dyskinesia with Hydrocephalus: A Case Report from Japan.

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by motile cilia dysfunction, mostly inherited in an autosomal recessive or X-linked manner. We herein report a 29-year-old woman with PCD caused by a heterozygous frameshift mutation due to a single nucleotide deletion in exon 3 of FOXJ1. Heterozygous de novo mutations in FOXJ1 have been reported as an autosomal-dominant cause of PCD.

Host-pathogen relationship in retreated tuberculosis with major rifampicin resistance-conferring mutations.

Introduction: It is assumed that host defense systems eliminating the pathogen and regulating tissue damage make a strong impact on the outcome of tuberculosis (TB) disease and that these processes are affected by rifampicin (RIF) resistance-conferring mutations of (Mtb). However, the host responses to the pathogen harboring different mutations have not been studied comprehensively in clinical settings. We analyzed clinico-epidemiological factors and blood transcriptomic signatures associated with major mutations conferring RIF resistance in a cohort study.

Transcription factor MAFB controls type I and II interferon response-mediated host immunity in -infected macrophages.

, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, has been identified as a candidate gene for early tuberculosis (TB) onset in Thai and Japanese populations. Here, we investigated the genome-wide transcriptional profiles of MAFB-knockdown (KD) macrophages infected with () to highlight the potential role of MAFB in host immunity against TB. Gene expression analysis revealed impaired type I and type II interferon (IFN) responses and enhanced oxidative phosphorylation in MAFB-KD macrophages infected with .

Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with .

Infection with leads to the development of tuberculosis (TB) with the formation of granulomatous lesions. Foamy macrophages (FM) are a hallmark of TB granulomas, because they provide the primary platform of proliferation and the main source of caseous necrosis. In this study, we applied spatial multiomic profiling to identify the signatures of FM within the necrotic granulomas developed in a mouse model resembling human TB histopathology.

Novel Screening System of Virulent Strains for the Establishment of a Complex Lung Disease Mouse Model Using Whole-Genome Sequencing.

The establishment of animal models reflecting human Mycobacterium avium complex (MAC) lung disease (LD) pathology has the potential to expand our understanding of the disease pathophysiology. However, inducing sustained infection in immunocompetent mice is difficult since MAC generally shows less virulence and higher genetic variability than M. tuberculosis.

Phenotypic and genotypic features of the Mycobacterium tuberculosis lineage 1 subgroup in central Vietnam.

Mycobacterium tuberculosis (Mtb) has different features depending on different geographic areas. We collected Mtb strains from patients with smear-positive pulmonary tuberculosis in Da Nang, central Vietnam. Using a whole genome sequencing platform, including genome assembly complemented by long-read-sequencing data, genomic characteristics were studied.

Proteomic Profiling Reveals the Architecture of Granulomatous Lesions Caused by Tuberculosis and Complex Lung Disease.

Tuberculosis (TB) and complex lung disease (MAC-LD) are both characterized pathologically by granuloma lesions, which are typically composed of a necrotic caseum at the center surrounded by fibrotic cells and lymphocytes. Although the histological characterization of TB and MAC-LD granulomas has been well-documented, their molecular signatures have not been fully evaluated. In this research we applied mass spectrometry-based proteomics combined with laser microdissection to investigate the unique protein markers in human mycobacterial granulomatous lesions.

Genotyping of Mycobacterium tuberculosis spreading in Hanoi, Vietnam using conventional and whole genome sequencing methods.

Hanoi is the capital of Vietnam, one of the 30 countries with a high tuberculosis (TB) burden. Fundamental data on the molecular epidemiology of the disease is required for future TB management. To identify lineages and genotypes of Mycobacterium tuberculosis (Mtb), conventional genotyping data from clinical isolates of the Hanoi area was compared with whole genome sequencing (WGS) analysis from 332 of 470 samples.

Primary ciliary dyskinesia caused by a large homozygous deletion including exons 1-4 of DRC1 in Japanese patients with recurrent sinopulmonary infection.

Background: Diffuse panbronchiolitis (DPB) is a sinopulmonary disease mainly affecting Asian populations. Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder impairing ciliary structure and function. These two disorders are not easily distinguished by clinical signs and symptoms.

Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam.

Drug-resistant tuberculosis (TB) is a serious global problem, and pathogen factors involved in the transmission of isoniazid (INH)-resistant TB have not been fully investigated. We performed whole genome sequencing of 332 clinical Mycobacterium tuberculosis (Mtb) isolates collected from patients newly diagnosed with smear-positive pulmonary TB in Hanoi, Vietnam. Using a bacterial genome-wide approach based on linear mixed models, we investigated the associations between 31-bp k-mers and clustered strains harboring katG-S315T, a major INH-resistance mutation in the present cohort and in the second panel previously published in South Africa.

Membrane-associated mucins of the ocular surface: New genes, new protein functions and new biological roles in human and mouse.

The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world.

Primary ciliary dyskinesia in Japan: systematic review and meta-analysis.

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder. Although the genetic tests and new diagnostic algorithms have recently been recommended, clinical signs and electron microscope (EM) findings have historically been the mainstays of diagnosis in Asia. To characterize PCD previously reported in Japan, we conducted a systematic review and meta-analysis.

Recurring large deletion in DRC1 (CCDC164) identified as causing primary ciliary dyskinesia in two Asian patients.

Background: Primary ciliary dyskinesia (PCD) is a relatively rare autosomal recessive or X-linked disorder affecting ciliary function. In the set of causative genes, however, predominant pathogenic variants remain unknown in Asia.

Method: A diagnosis of PCD was made following a modern comprehensive testing including genetic analysis; targeted resequencing for screening variants, and Sanger sequencing for determination of the breakpoints, with an additional review of databases to calculate the deletion frequency.

Spoligotyping and whole-genome sequencing analysis of lineage 1 strains of Mycobacterium tuberculosis in Da Nang, Vietnam.

Background: Spacer oligonucleotide typing (spoligotyping), a widely used, classical genotyping method for Mycobacterium tuberculosis complex (MTBC), is a PCR-based dot-blot hybridization technique to detect the genetic diversity of the direct repeat (DR) region. Of the seven major MTBC lineages in the world, lineage 1 (Indo-Oceanic) mostly corresponds to the East African-Indian (EAI) spoligotype family in East Africa and Southeast Asia.

Objectives: We investigated the genomic features of Vietnamese lineage 1 strains, comparing spoligotype patterns using whole-genome sequencing (WGS) data.

Complete Genome Sequences of Three Representative Beijing Family Strains Belonging to Distinct Genotype Clusters in Hanoi, Vietnam, during 2007 to 2009.

We present here three complete genome sequences of Beijing family strains isolated in Hanoi, Vietnam. These three strains were selected from major genotypic clusters (15-MIRU-VNTR) identified in a previous population-based study. We emphasize their importance and potential as reference strains in this Asian region.

Complete Genome Sequence of a Strain Belonging to the East African-Indian Family in the Indo-Oceanic Lineage, Isolated in Hanoi, Vietnam.

The East African-Indian (EAI) family of is an endemic group mainly observed in Southeast Asia. Here, we report the complete genome sequence of an strain isolated as a member of the EAI family in Hanoi, Vietnam, a country with a high incidence of tuberculosis.

Circulating granulysin levels in healthcare workers and latent tuberculosis infection estimated using interferon-gamma release assays.

Background: Granulysin (GNLY) is produced by human lymphocyte subpopulations and exhibits antimicrobial activity against Mycobacterium tuberculosis. We examined the association between GNLY levels in blood and latent tuberculosis (TB) infection.

Methods: Latency of TB infection among Vietnamese healthcare workers was estimated using interferon-gamma release assays (IGRA), and serum GNLY concentrations were measured using enzyme-linked immunosorbent assays.