Hyaluronidase 2 deficiency due to novel compound heterozygous variants in HYAL2: a case report of siblings with HYAL2 deficiency showing different clinical severity and literature review.

This study reports the first Asian case of syndromic cleft lip and palate resembling CHARGE-like syndrome, caused by novel compound heterozygous variants of the HYAL2 gene. Hyaluronidase-2 (HYAL2) plays a critical role in hyaluronic acid degradation and tissue remodelling. A 2-year-old Japanese boy presented with growth deficiency, congenital heart disease, craniofacial dysmorphism, micropenis, and developmental delays-features that overlapped with those of CHARGE syndrome.

Analysis of Functional cis-Regulatory Elements Reveals Novel Transcriptional Regulatory Mechanisms in Gonadal Development.

Introduction: Recent studies have demonstrated that the production of bidirectional enhancer-derived transcripts (eRNAs) is a characteristic of an active cis-regulatory element (CRE). Higher levels of eRNAs synthesis correlate with the activation of histone modifications, a potentially valuable tool for deciphering the complexity of the gene regulatory network.

Method: To understand the changes of CREs during gonadal development in mice, we collected gonadal WT1-positive cells from the piggyBac-Wt1-mCherry-2A-EGFP (PBWt1-RG) reporter strain at E13.

A MinION-based Long-Read Sequencing Application With One-Step PCR for the Genetic Diagnosis of 21-Hydroxylase Deficiency.

Context: Recently developed long-read sequencing (LRS) technology has been considered an option for CYP21A2 analysis. However, the clinical use of LRS for CYP21A2 analysis is limited.

Objective: This study's objective is to develop an efficient and low-cost LRS system for CYP21A2 screening.

BMP2 is a potential causative gene for isolated dextrocardia situs solitus.

BMP2 (bone morphogenic protein-2) is a member of the TGF-β superfamily and has essential roles in the development of multiple organs, including osteogenesis. Because of its crucial role in organ and skeletal development, Bmp2 null mice is fetal lethal. The recent report has characterized multiple patients with BMP2 haploinsufficiency, describing individuals with BMP2 sequence variants and deletions associated with short stature without endocrinological abnormalities, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease.

Phenotypic Variation in 46,XX Disorders of Sex Development due to the Fourth Zinc Finger Domain Variant of WT1: A Familial Case Report.

Introduction: The variants in the zinc finger (ZF) domains 1-3 in WT1 are one of the major causes of 46,XY disorders of sex development (DSD). Recently, variants in the fourth ZF (ZF4 variants) were reported to cause 46,XX DSD. However, all the 9 patients reported were de novo, and no familial cases were identified.

A novel variant of NR5A1, p.R350W implicates potential interactions with unknown co-factors or ligands.

Introduction: NR5A1 and NR5A2 belong to an orphan nuclear receptor group, and approximately 60% of their amino acid sequences are conserved. Transcriptional regulation of NR5A receptors depends on interactions with co-factors or unidentified ligands.

Purpose And Methods: We employed in vitro and in silico analysis for elucidating the pathophysiology of a novel variant in the ligand-binding domain of NR5A1, p.

Clinical report: Chronic liver dysfunction in an individual with an AMOTL1 variant.

AMOTL1 is a member of the Motin protein family and localizes to tight junctions and is involved in cell polarity and paracellular permeability. Pathological variants have been reported in three patients from two separate families in recent years. The clinical spectrum includes cleft lip and palate along with a high incidence of congenital cardiac disease and ear malformations.

The High Relevance of 21-Deoxycortisol, (Androstenedione + 17α-Hydroxyprogesterone)/Cortisol, and 11-Deoxycortisol/17α-Hydroxyprogesterone for Newborn Screening of 21-Hydroxylase Deficiency.

Context: There are limited reports on the detailed examination of steroid profiles for setting algorithms for 21-hydroxylase deficiency (21OHD) screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Objective: We aimed to define an algorithm for newborn screening of 21OHD by LC-MS/MS, measuring a total of 2077 dried blood spot samples in Tokyo.

Methods: Five steroids (17α-hydroxyprogesterone [17αOHP], 21-deoxycortisol [21DOF], 11-deoxycortisol [11DOF], androstenedione [4AD], and cortisol [F]) were included in the panel of LC-MS/MS.

Two ovarian candidate enhancers, identified by time series enhancer RNA analyses, harbor rare genetic variations identified in ovarian insufficiency.

The genetic regulation of ovarian development remains largely unclear. Indeed, in most cases of impaired ovarian development-such as 46,XX disorders of sex development (DSD) without SRY, and premature ovarian insufficiency (POI)-the genetic causes have not been identified, and the vast majority of disease-associated sequence variants could lie within non-coding regulatory sequences. In this study, we aimed to identify enhancers of five ovarian genes known to play key roles in early ovarian development, basing our analysis on the expression of enhancer derived transcripts (eRNAs), which are considered to characterize active enhancers.

Adrenal suppression and anthropometric data at two years of age was not influenced by the initial hydrocortisone dose in patients with 21-hydroxylase deficiency.

In contrast to the glucocorticoid maintenance therapy employed in patients with 21 hydroxylase deficiency (21OHD), the initial therapy remains to be optimized. The Japanese Society for Pediatric Endocrinology recommends a hydrocortisone (HC) dose of 25-100 mg/m, which is higher than that employed in Western countries. Herein, we aimed to retrospectively verify the impact of initial HC treatment during infancy and early childhood.

Marked clinical heterogeneity in congenital hyperinsulinism due to a novel homozygous ABCC8 mutation.

Background: The most severe forms of congenital hyperinsulinism (CHI) are caused by inactivating mutations of two KATP channel genes, KCNJ11 and ABCC8. Unresponsiveness to diazoxide and need for subtotal pancreatectomy can usually be predicted by genetic form, particularly biallelic mutations in KATP channel genes. A few reports indicated marked clinical heterogeneity in siblings with identical biallelic mutations in ABCC8.

The progression of salt-wasting and the body weight change during the first 2 weeks of life in classical 21-hydroxylase deficiency patients.

Background: One of the major purposes of newborn screening for 21-hydroxylase deficiency (21OHD) is preventing life-threatening adrenal crisis. However, the details of adrenal crisis in newborns are not precisely documented.

Aim: We aimed to clarify the clinical details of salt-wasting in newborn 21OHD patients.

Prematurity at less than 24 weeks of gestation is a risk for prolonged hyperglycemia in extremely low-birth weight infants.

Hyperglycemia in extremely low-birth weight infants (ELBWIs) is frequently observed during the acute perinatal phase, (i.e., first 1-2 weeks postnatal period); however it can occasionally persists for >2 weeks, extending to the post-acute phase.

Risk of coronary artery lesions in young infants with Kawasaki disease: need for a new diagnostic method.

Aim: To examine clinical characteristics of Kawasaki disease (KD) in infants younger than 3 months of age and to develop a method for detecting KD in febrile infants.

Method: In a case-control study, we retrospectively collected clinical and laboratory data from 24 KD infants younger than 3 months of age out of 410 KD patients. We then compared younger infants with both older patients and febrile infants with respiratory syncytial virus (RSV) infection and urinary tract infections (UTI).

Initial patient choice of a growth hormone device improves child and adolescent adherence to and therapeutic effects of growth hormone replacement therapy.

Background: It is thought that growth hormone (GH) therapy success depends on the patient's adherence to their treatment regimen, but an optimal approach to improve adherence has not yet been established.

Methods: To evaluate the effect of patient choice of a GH device on adherence to GH therapy, we carried out a retrospective longitudinal study of 46 GH deficient patients (24 boys, mean age of commencing GH therapy: 7.70±3.