BackgroundWe intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate.MethodsWe assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software. Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Each case was further discussed in a monthly consensus meeting that included the participation of all laboratory personnel, bioinformaticians, geneticists, and clinicians.ResultsThe NGS panel identified 28 patients (37.8%) with genetic abnormalities; 25 patients had pathogenic or likely pathogenic SNVs in 17 genes including SXTBP1 (n = 3), CDKL5 (n = 2), KCNQ2 (n = 2), SCN1A (n = 2), SYNGAP1 (n = 2), GNAO1 (n = 2), KCNT1 (n = 2), BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 (n = 1). The other 3 patients had pathogenic CNVs (2 duplications and 1 deletion) with varying sizes (from 2.5 Mb to 12 Mb). The overall diagnostic yield was 37.8% after following our step-by-step approach for clinical consensus.ConclusionsNGS is a useful diagnostic tool with great utility for patients with EOE. Diagnostic yields can be maximized with a standardized and team-based approach.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0320-7) contains supplementary material, which is available to authorized users.
These data showed that obese men with sarcopenia exhibited a significantly higher IR risk than obese, nonsarcopenic men. In women, body composition did not affect IR if they were already obese.
Aims Early identification of individuals with insulin resistance (IR) and metabolically unhealthy state can help prevent various diseases and improve quality of life. In this study, we investigated a possible marker of IR and metabolic health status, alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio, and aimed to confirm its feasibility in a large population study.
Methods A total of 16,371 adults from Korean National Health and Examination Survey were studied. Participants were divided into four groups according to their ALT/AST ratio quartiles. The homeostatic model assessment of insulin resistance level and proportion of people with IR, impaired fasting glucose, and undiagnosed type 2 diabetes were compared for each group. Receiver-operating characteristics (ROC) curve was also used to assess the usefulness of ALT/AST ratio to identify individuals with IR and metabolically unhealthy.
Results In the groups with higher ALT/AST ratio, HOMA-IR level, proportion of IR, and proportion of individuals with IFG or type 2 diabetes mellitus was higher than that in those with low ALT/AST ratio. When analyzed with other factors related to IR, the data showed that the ALT/AST ratio was an independent predictor of IR (odds ratio 1.363, 95% confidential interval 1.323–1.405, p<0.001). When ROC curve analysis was done, area under curve (AUC) for identifying individuals with IR was 0.634. In addition, metabolically unhealthy individuals showed significantly higher ALT/AST ratio than metabolically healthy individuals (0.9780 vs 0.8511, p<0.001).
Conclusions ALT/AST ratio was well-correlated with IR, IR-related conditions, and metabolic health status. This easily accessible method to estimate IR may facilitate the early screening of IR, which can result in prevention of IR-related morbid conditions.
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