Genetic landscape in undiagnosed patients with syndromic hearing loss revealed by whole exome sequencing and phenotype similarity search.

There are hundreds of rare syndromic diseases involving hearing loss, many of which are not targeted for clinical genetic testing. We systematically explored the genetic causes of undiagnosed syndromic hearing loss using a combination of whole exome sequencing (WES) and a phenotype similarity search system called PubCaseFinder. Fifty-five families with syndromic hearing loss of unknown cause were analyzed using WES after prescreening of several deafness genes depending on patient clinical features.

Practical guide for the diagnosis and management of primary ciliary dyskinesia.

Objective: Primary ciliary dyskinesia (PCD) is a relatively rare genetic disorder that affects approximately 1 in 20,000 people. Approximately 50 genes are currently known to cause PCD. In light of differences in causative genes and the medical system in Japan compared with other countries, a practical guide was needed for the diagnosis and management of Japanese PCD patients.

Pediatric allergies in Japan: Coronavirus disease pandemic-related risk factors.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted various parts of society, including Japanese children with allergies.

Objective: This study investigated risk factors for pediatric allergic diseases associated with the state of emergency owing to the COVID-19 pandemic in Japan, including during school closures.

Methods: Parents of pediatric patients (0-15 years) with allergies were enrolled and queried regarding the impact of school closure on pediatric allergies compared to that before the COVID-19 pandemic.

Development of an Oral Immunotherapy-Related Parental Burden Scale.

Introduction: Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems.

Parents' Fears about Hospital Visits and Trait Anxiety in the COVID-19 Pandemic.

Anxiety in parents of children with allergic diseases during the COVID-19 pandemic may impact hospital visits. This study explored the effect of the pandemic on parents' fears about hospital visits and their relationship with their personality traits. A cross-sectional, questionnaire-based study was conducted between September 2020 and March 2021, with parents of children aged 0-15 years, who regularly visited 24 outpatient facilities for allergic disease.

Pharmacotherapy focusing on for the management of otitis media with effusion in children: Systematic review and meta-analysis.

Objective: To examine the evidence for treating children with otitis media with effusion with pharmacotherapy.

Data Sources: For the systematic review, data were retrieved from PubMed, Cochrane database, and the Japan Medical Abstracts Society Database (1st January 1995 through 31th May 2019).

Study Selection: Articles addressing pharmacotherapy for the management of otitis media with effusion in children were selected in English.

Whole exome analysis of patients in Japan with hearing loss reveals high heterogeneity among responsible and novel candidate genes.

Background: Heterogeneous genetic loci contribute to hereditary hearing loss; more than 100 deafness genes have been identified, and the number is increasing. To detect pathogenic variants in multiple deafness genes, in addition to novel candidate genes associated with hearing loss, whole exome sequencing (WES), followed by analysis prioritizing genes categorized in four tiers, were applied.

Results: Trios from families with non-syndromic or syndromic hearing loss (n = 72) were subjected to WES.

Phenotype-genotype correlation in patients with typical and atypical branchio-oto-renal syndrome.

Some patients have an atypical form of branchio-oto-renal (BOR) syndrome, which does not satisfy the diagnostic criteria, despite carrying a pathogenic variant (P variant) or a likely pathogenic variant (LP variant) of a causative gene. P/LP variants phenotypic indices have yet to be determined in patients with typical and atypical BOR syndrome. We hypothesized that determining phenotypic and genetic differences between patients with typical and atypical BOR syndrome could inform such indices.

A High Risk of Missing Congenital Cytomegalovirus-Associated Hearing Loss through Newborn Hearing Screening in Japan.

It remains unclear to what extent newborn hearing screening (NHS) detects congenital cytomegalovirus (cCMV)-associated sensorineural hearing loss (SNHL) in Japan. This study aimed to clarify the NHS results and audiological characteristics of patients with cCMV-associated SNHL. A total of 541 individuals with unilateral or bilateral hearing loss of unknown etiology were examined for cCMV infection.

Progress of Home-Based Food Allergy Treatment during the Coronavirus Disease Pandemic in Japan: A Cross-Sectional Multicenter Survey.

The coronavirus disease 2019 (COVID-19) pandemic's impact on food allergy treatment such as home-based oral immunotherapy (OIT) is not known. This cross-sectional, questionnaire-based anonymized survey screened 2500 parents of children with allergic diseases and was conducted in the pediatric outpatient clinics of 24 hospitals. Basic clinical data of the children were collected along with the degree of allergy control, parental anxiety about emergency visits, and the risk of COVID-19 in the first state of emergency.

The influence of tonsillectomy on allergic diseases in pediatric patients.

Background: The influence of tonsillectomy on allergic airway diseases is not well known.

Objectives: In the present study, the influence of tonsillectomy on perennial allergic rhinitis (PAR) and bronchial asthma (BA) among pediatric subjects was prospectively investigated.

Methods: The tonsillectomy (surgery group) and the age-matched non-surgical subjects (control group) were examined and followed prospectively.

Differences in hearing levels between siblings with hearing loss caused by GJB2 mutations.

Objective: Hearing loss caused by GJB2 mutations is inherited in an autosomal recessive manner (DFNB1); thus siblings of an affected child have a 25% chance of also being affected. Hearing loss among subsequent siblings carrying the same GJB2 mutation is a concern for parents and a frequent topic of enquiry during genetic counseling. Evidence exists for genotype-phenotype correlations of GJB2 mutations; however, no analysis of differences in hearing among siblings, in whom the common genetic background may decrease variation, has been reported.

Deterioration in Distortion Product Otoacoustic Emissions in Auditory Neuropathy Patients With Distinct Clinical and Genetic Backgrounds.

Objectives: Auditory neuropathy (AN) is a clinical disorder characterized by the absence of auditory brainstem response and presence of otoacoustic emissions. A gradual loss of otoacoustic emissions has been reported for some cases of AN. Such cases could be diagnosed as cochlear hearing loss and lead to misunderstanding of the pathology when patients first visit clinics after the loss of otoacoustic emissions.

High-level heteroplasmy for the m.7445A>G mitochondrial DNA mutation can cause progressive sensorineural hearing loss in infancy.

Objective: Hearing loss caused by mutation of mitochondrial DNA typically develops in late childhood or early adulthood, but rarely in infancy. We report the investigation of a patient to determine the cause of his early onset hearing loss.

Materials And Methods: The proband was a boy aged 1 year and 2 months at presentation.

Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss.

Background: To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL.

The Improvement of the Hepatic Histological Findings in a Patient with Non-alcoholic Steatohepatitis with Type 2 Diabetes after the Administration of the Sodium-glucose Cotransporter 2 Inhibitor Ipragliflozin.

The patient was a 67-year-old woman with type 2 diabetes and non-alcoholic steatohepatitis (NASH). The administration of the sodium-glucose cotransporter 2 (SGLT2) inhibitor, ipragliflozin improved her liver dysfunction clinically and histologically. The serum alanine aminotransferase (ALT) and ferritin levels decreased to normal limits after treatment for four months.

The first sporadic case of DFNA11 identified by next-generation sequencing.

We report the first sporadic case of nonsyndromic autosomal dominant hearing loss (DFNA11). The patient was a 5-year-old boy with moderate bilateral hearing loss. Targeted next-generation sequencing analysis of patient DNA identified a known heterozygous DFNA11 mutation, c.

Efficacy and safety of oral propranolol for infantile hemangioma in Japan.

Background: There have been few reports on the efficacy and safety of oral propranolol at 3 mg/kg/day for infantile hemangioma (IH) in Japanese patients.

Methods: A multicenter, open-label phase III study was conducted to evaluate the efficacy and safety of oral propranolol solution in Japanese infants aged 35-150 days with proliferating IH. Thirty-two patients were enrolled in the study, received propranolol solution for 24 weeks at 3 mg/kg/day, and completed the study.

Analysis of Streptococcus pneumoniae and Haemophilus influenzae isolated from middle ear fluid before and after the introduction of government subsidies for pneumococcal and H. influenzae type b vaccines in Japan.

This study aimed to identify trends in frequency, serotype, and antimicrobial susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolated from middle ear fluid specimens of children aged≤15 years (mean, 2 years), before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and the H. influenzae type b vaccine, at a pediatric facility in Japan. Sixty-six S.

Frequency and specific characteristics of the incomplete partition type III anomaly in children.

Objectives/hypothesis: To determine the frequency of the incomplete partition type III anomaly and the genetic and clinical features associated with POU3F4 mutations in children with hearing loss.

Study Design: Retrospective case series from 2000 to 2014 at the National Hospital Organization Tokyo Medical Center and collaborating hospitals.

Methods: A total of 1,004 patients (from 938 families) who had hearing loss by 10 years of age and had undergone computed tomography scanning of their temporal bones were enrolled in this genetic, clinical, and radiological study.

A novel frameshift variant of COCH supports the hypothesis that haploinsufficiency is not a cause of autosomal dominant nonsyndromic deafness 9.

COCH (coagulation factor C homology) encodes cochlin, and certain mutations of COCH cause autosomal dominant nonsyndromic deafness 9 (DFNA9). Hearing loss due to COCH mutation begins in adulthood, and 17 missense mutations and two in-frame mutations have been reported. Studies with animal and cellular models have suggested that the underlying biological mechanism of DFNA9 is the dominant-negative effect of mutated COCH and not haploinsufficiency.

High prevalence of CDH23 mutations in patients with congenital high-frequency sporadic or recessively inherited hearing loss.

Background: Mutations in CDH23 are responsible for Usher syndrome 1D and recessive non-syndromic hearing loss. In this study, we revealed the prevalence of CDH23 mutations among patients with specific clinical characteristics.

Methods: After excluding patients with GJB2 mutations and mitochondrial m.