B-cell immunodeficiency associated with polynucleotide kinase 3'-phosphatase (PNKP) deficiency.

Background: DNA repair is crucial for maintaining genomic integrity and plays a significant role in the immune system. Defects in DNA repair pathways are often associated with immunodeficiency, including B-cell defects, which are consistent with the need for DNA repair during V(D)J recombination, class switching, and somatic hypermutation during B-cell maturation. Polynucleotide kinase 3'-phosphatase (PNKP) plays a significant role in DNA repair.

Genotype-phenotype correlations and phenotypic expansion in a case series of ReNU syndrome associated with variants.

encodes U4 small nuclear RNA (snRNA), a non-coding RNA forming the spliceosome complex via the U4/U6 snRNA duplex. heterozygous variants cause ReNU syndrome, which is characterised by intellectual disability, developmental delay, epilepsy, short stature and distinctive dysmorphic features. ReNU syndrome accounts for 0.

Two distinct phenotypes in Snijders Blok-Campeau syndrome and characterization of the behavioral phenotype in a zebrafish model.

Chromatin remodeling is an important system controlling gene expression. CHD3, which is a causative gene of Snijders Blok-Campeau syndrome (SNIBCPS), is a member of the chromodomain helicase DNA-binding (CHD) family related to chromatin remodeling. SNIBCPS is characterized by developmental delay (DD), intellectual disability (ID), macrocephaly, and facial features including a prominent forehead and hypertelorism.

Severe pharyngeal stenosis and laryngomalacia in an individual of HNRNPU-related neurodevelopmental disorder associated with a novel nonsense variant.

Heterozygous loss-of-function variants in heterogeneous nuclear ribonucleoprotein U (HNRNPU) cause early-onset developmental and epileptic encephalopathy with multiple congenital anomalies. Limited clinical information is currently available on HNRNPU-related neurodevelopmental disorder. The patient was a 1-year-old Japanese girl with developmental delay, hypotonia, early-onset epilepsy, respiratory distress, and distinctive facial features, including ptosis, epicanthus, a prominent nasal bridge, a wide nasal floor, a cleft soft palate, and micrognathia.

Chimerism analysis by ABO blood group genotyping with digital droplet PCR.

Objective: Chimerism analysis is an important post-transplant assessment for allogeneic hematopoietic stem cell transplant (HCT) recipients. Although various chimerism analysis techniques are already established, they are limited in terms of sensitivity, versatility, and turnaround time. Our objective was to develop a digital droplet polymerase chain reaction (ddPCR) assay for chimerism analysis using ABO gene polymorphisms as markers.

Biallelic TXNDC15 variants associated with Joubert syndrome-related molar tooth sign and forebrain malformation.

TXNDC15 encodes thioredoxin domain-containing protein 15, a protein disulfide isomerase that plays a role in ciliogenesis. Biallelic TXNDC15 variants have been reported in six individuals of Meckel syndrome (MKS) with perinatal lethal phenotypes, but have not been reported in patients with Joubert syndrome (JS). Here, we describe a 1-year-old female patient with compound heterozygous TXNDC15 variants demonstrating cerebellar vermis hypoplasia with the molar tooth sign, mild holoprosencephaly, and cortical abnormalities.

Noonan syndrome-like phenotype associated with an ERF frameshift variant.

Noonan syndrome is a so-called "RASopathy," that is characterized by short stature, distinctive facial features, congenital heart defects, and developmental delay. Of individuals with a clinical diagnosis of Noonan syndrome, 80%-90% have pathogenic variants in the known genes implicated in the disorder, but the molecular mechanism is unknown in the remaining cases. Heterozygous pathogenic variants of ETS2 repressor factor (ERF), which functions as a repressor in the RAS/MAPK signaling pathway, cause syndromic craniosynostosis.

Role of TOE1 variants at the nuclear localization motif in pontocerebellar hypoplasia 7.

Biallelic TOE1 variants can cause pontocerebellar hypoplasia type 7 (PCH7), a condition characterized by pontocerebellar hypoplasia with genital abnormality. TOE1 is a 3'-exonuclese for 3'-end maturation in small nuclear RNA. TOE1 pathogenic variants have been reported at the DEDD catalytic domain and zinc finger motif.

A CAMK2B variant associated with tetralogy of Fallot, developmental delay, and growth retardation.

CAMK2B encodes the beta-subunit of calcium/calmodulin-dependent protein kinase II (CAMKII), which is expressed mainly in the brain. Variants of CAMK2A and CAMK2B cause neurodevelopmental disorders, and CAMK2B alterations have been described in at least 14 patients with intellectual disability and developmental delay. Here, we describe a novel CAMK2B variant in a patient with tetralogy of Fallot (TOF), developmental delay, and growth retardation.

A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors.

The feasibility of a short-term, three-dimensional (3D) culture-based drug sensitivity test (DST) for surgically resected malignant bone tumors, including osteosarcoma (OS), was evaluated utilizing two OS cell line (KCS8 or KCS9)-derived xenograft (CDX) models. Twenty-three (KCS8) or 39 (KCS9) of 60 tested drugs were likely effective in OS cells derived from a cell line before xenografting. Fewer drugs (19: KCS8, 26: KCS9) were selected as effective drugs in cells derived from a CDX tumor, although the drug sensitivities of 60 drugs significantly correlated between both types of samples.

A Japanese patient with Teebi hypertelorism syndrome and a novel CDH11 EC1 domain variant.

The gene CDH11 encodes cadherin-11, a Type II cadherin superfamily member that contains five extracellular cadherin (EC) domains. Cadherin-11 undergoes trans-dimerization via the EC1 domain to generate cadherin complexes. Compound heterozygous and homozygous loss-of-function CDH11 variants are observed in Elsahy-Waters syndrome (EWS), which shows characteristic craniofacial features, vertebral abnormalities, cutaneous syndactyly in 2-3 digits, genitourinary anomalies, and intellectual disability.

Safety, efficacy and pharmacokinetics of palivizumab in off-label neonates, infants, and young children at risk for serious respiratory syncytial virus infection: a multicenter phase II clinical trial.

Background: Pediatric patients with certain rare diseases are at increased risk of severe respiratory syncytial virus (RSV) infection. However, the prophylactic use of anti-RSV antibody (palivizumab) in these patients is not indicated at present in Japan.

Methods: This first-in-the-world multicenter, uncontrolled, open-label, phase II clinical trial was carried out between 28 July 2019 and 24 September 2021 at seven medical institutions in Japan to investigate the efficacy, safety, and pharmacokinetics of palivizumab in 23 subjects recruited from among neonates, infants, or children aged 24 months or younger who had any of the following conditions: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease.

Complex congenital cardiovascular anomaly in a patient with AGO1-associated disorder.

Pathogenic AGO1 variants have been associated with neurodevelopmental disorders, including autism spectrum disorder, developmental delay, intellectual disability, and dysmorphic facial appearance. In mammalian models, defects in microRNA (miRNA) biogenesis are associated with congenital heart disease and dilated cardiomyopathy. We describe the case of a patient with partial anomalous pulmonary venous return, hypoplastic left lung, bilateral pulmonary sequestration, and dilated myocardiopathy.