Next-generation sequencing (NGS) and array-based comparative genomic hybridization (array CGH) have enabled us to perform high-throughput mutation screening and genome-wide copy number analysis, respectively. These methods can be used for molecular diagnosis of pediatric endocrine disorders. NGS has determined the frequency and phenotypic variation of mutations in several disease-associated genes. Furthermore, whole exome analysis using NGS has successfully identified several novel causative genes for endocrine disorders. Array CGH is currently used as the standard procedure for molecular cytogenetic analysis. Array CGH can detect various submicroscopic genomic rearrangements involving exons or enhancers of disease-associated genes. This review introduces some examples of the use of NGS and array CGH for the molecular diagnosis of pediatric endocrine disorders.
Comparative Genomic Hybridization* ; Cytogenetic Analysis ; Diagnosis* ; Exome ; Exons ; Mass Screening

Recent advances in long-read next-generation sequencing (NGS) have enabled researchers to identify several pathogenic variants overlooked by short-read NGS, array-based comparative genomic hybridization, and other conventional methods. Long-read NGS is particularly useful in the detection of structural variants and repeat expansions. Furthermore, it can be used for mutation screening in difficultto- sequence regions, as well as for DNA-methylation analyses and haplotype phasing. This mini-review introduces the usefulness of long-read NGS in the molecular diagnosis of pediatric endocrine disorders.

Disorder of Sex Development, 46,XY/genetics* ; GATA4 Transcription Factor/genetics* ; Genetic Testing ; Heart Defects, Congenital ; Humans ; Male ; Molecular Structure ; Mutation/genetics*

BACKGROUND: There is little data on the association between the lower nutrition represented by serum albumin levels and related factors in a general population. The present study aimed to determine whether the albumin level positioned as some kind of biomarker with frailty measures, trace elements, and an inflammation marker. METHODS: In 2018, we performed an epidemiological survey in 1368 subjects who resided in Tanushimaru, Japan, in which we examined the blood chemistry including albumin, trace elements, hormone levels, and carotid ultrasonography. Albumin levels were categorized into 4 groups (G1 [3.2-3.9 mg/dL], G2 [4.0-4.3 mg/dL], G3 [4.4-4.6 mg/dL], and G4 [4.7-5.3 mg/dL]). The participants underwent measurements of handgrip strength and were tested by asking to walk 5 m. Their cognitive functions were evaluated by the mini-mental state examination (MMSE). RESULTS: Multiple stepwise regression analysis demonstrated that albumin levels were significantly and independently associated with age (inversely), systolic blood pressures, estimated glomerular filtration rate (eGFR), MMSE score, frailty measures (handgrip strength), an inflammation marker (high-sensitivity C-reactive protein), hormones (growth hormone (inversely) and insulin-like growth factor-1), and trace elements (calcium, magnesium, iron, and zinc), with a linear trend. CONCLUSIONS Lower albumin levels, even in the normal range, were found to be related factors of frailty measures, trace elements, and an inflammation marker in a general population.
Aged ; Albumins/metabolism* ; Biomarkers/blood* ; Cross-Sectional Studies ; Female ; Frailty/physiopathology* ; Hand Strength/physiology* ; Humans ; Inflammation/blood* ; Japan ; Male ; Trace Elements/blood*

BACKGROUND: Remnant-like particle cholesterol (RLP-C) is highly atherogenic, which is associated with atherosclerosis. However, RLP-C has not been routinely measured in the clinical practice. We estimated RLP-C levels using conventional lipid profiles and examined the association between estimated RLP-C and related factors including nutrient intake. METHODS: This study was performed in Uku town, Nagasaki prefecture, Japan in 2019. A total of 225 subjects were enrolled and directly measured RLP-C levels. Estimated RLP-C levels were defined as the following formula [total cholesterol - (LDL-cholesterol) - (HDL-cholesterol)]. Multivariate analyses were used to assess the relationship between estimated RLP-C and atherogenic factors. We calculated cut-off values on dichotomized RLP-C (< 7.5 mg/dL vs. ≥ 7.5 mg/dL) by receiver operating characteristic (ROC) curve. RESULTS: The mean values of directly measured RLP-C levels and estimated RLP-C were 4.0 mg/dL and 16.4 mg/dL, respectively. In the multiple stepwise linear regression analysis, directly measured and estimated RLP-C levels were independently and commonly associated with apolipoprotein E, triglycerides, and vegetable fat intake (inversely). Using ROC curves, we found the cut-off value of estimated RLP-C was 22.0 mg/dL. CONCLUSION We demonstrated that the estimated RLP-C levels using conventional lipid profiles may substitute for directly measured RLP-C and these levels were independently and inversely associated with vegetable fat intake in the community-dwelling Japanese population.
Aged ; Aged, 80 and over ; Cholesterol/blood* ; Dietary Fats/blood* ; Female ; Humans ; Japan ; Lipids/blood* ; Lipoproteins/blood* ; Male ; Middle Aged ; Triglycerides/blood* ; Vegetables