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[Whole exome sequencing analysis of compound heterozygous variants of CDAN1 gene in a Chinese family with non-immune hydrops fetalis].
Wang, Y, Li, Q, Sun, X, Li, S, He, J, Zhang, M, Huang, L, He, W
Nan fang yi ke da xue xue bao = Journal of Southern Medical University. 2021;(12):1899-1903
Abstract
OBJECTIVE To study the clinical characteristics and genetic variants in a family with non-immune hydrops fetalis. METHODS Peripheral blood samples were collected from a pregnant woman with suspected non-immune hydrops fetalis of the fetus for routine blood analysis, Rh typing and TORCH test. Amniotic fluid sample was collected for G-banded chromosomal karyotyping. The genomic DNA of the proband was extracted for analysis of chromosomal abnormalities using copy number variation sequencing. Whole-exome sequencing (Trios-WES) was performed on Illumina NovaSeq 6000 platform and exonic DNA was enriched using Agilent Sure Select XT Human All Exon V6. Sorting intolerant from tolerant (SIFT), I-mutant2, PolyPhen-2 and PROVEAN were used to predict the potential effects of amino acid substitution on protein function and splicing variation. The spatial structure of codanin-1 was modeled and visualized with Alpha Fold 2 and PyMOL 2.3 software, and the variants with potential clinical significance were confirmed by Sanger sequencing. RESULTS Fetal ultrasound at 17 weeks of gestation showed extensive subcutaneous edema, ascites, pleural effusion, enlarged liver and spleen, thickened placenta and pericardium defect. NGS reveals that proband has carried c.2140C>T, p.R714W, and c.1264_1265delCT, p.L422* compound heterozygous variants of CDAN1 gene, which were found to be pathogenic and inherited from proband's father and mother respectively. CONCLUSION We identified a novel heterozygous CDAN1 gene mutation causing fetal-onset congenital dyserythropoietic anemia type 1, which triggers non-immune hydrops fetalis.
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Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
Wen, W, Zheng, W, Okada, Y, Takeuchi, F, Tabara, Y, Hwang, JY, Dorajoo, R, Li, H, Tsai, FJ, Yang, X, et al
Human molecular genetics. 2014;(20):5492-504
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Abstract
Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.