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A novel compound heterozygous mutation in SLC5A2 contributes to familial renal glucosuria in a Chinese family, and a review of the relevant literature.
Li, S, Yang, Y, Huang, L, Kong, M, Yang, Z
Molecular medicine reports. 2019;(5):4364-4376
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Abstract
Familial renal glucosuria (FRG) is a rare condition that involves isolated glucosuria despite normal blood glucose levels. Mutations in the solute carrier family 5 member 2 (SLC5A2) gene, which encodes sodium‑glucose cotransporter 2 (SGLT2), have been reported to be responsible for the disease. Genetic testing of the SLC5A2 gene was conducted in a Chinese family with FRG. A number of online tools were used to predict the potential effect of the identified mutations on SGLT2 function. Additionally, the SLC5A2 mutations previously reported in PubMed were summarized. A novel compound heterozygous mutation (c.514T>C, p.W172R; c.1540C>T, p.P514S) of the SLC5A2 gene in a Chinese child with FRG was identified. In total, 86 mutations of the SLC5A2 gene have been reported to be associated with FRG. The novel compound heterozygous mutation (c.514T>C, p.W172R; c.1540C>T, p.P514S) of the SLC5A2 gene may be responsible for the onset of FRG. The present study provides a starting point for further investigation of the molecular pathogenesis of the SLC5A2 gene mutation in patients with FRG.
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Long-term follow-up in a Chinese child with congenital lipoid adrenal hyperplasia due to a StAR gene mutation.
Zhao, X, Su, Z, Liu, X, Song, J, Gan, Y, Wen, P, Li, S, Wang, L, Pan, L
BMC endocrine disorders. 2018;(1):78
Abstract
BACKGROUND Congenital lipoid adrenal hyperplasia (CLAH) is an extremely rare and the most severe form of congenital adrenal hyperplasia. Typical features include disorder of sex development, early-onset adrenal crisis and enlarged adrenal glands with fatty accumulation. CASE PRESENTATION We report a case of CLAH caused by mutations in the steroidogenic acute regulatory protein (StAR) gene. The patient had typical early-onset adrenal crisis at 2 months of age. She had normal-appearing female genitalia and a karyotype of 46, XY. The serum cortisol and adrenal steroids levels were always nearly undetectable, but the adrenocorticotropic hormone levels were extremely high. Genetic analysis revealed compound heterozygous mutations at c. 229C > T (p.Q77X) in exon 3 and c. 722C > T (p.Q258X) in exon 7 of the StAR gene. The former mutation was previously detected in only two other Chinese CLAH patients. Both mutations cause truncation of the StAR protein. The case reported here appears to be a classic example of CLAH with very small adrenal glands and is the second reported CLAH case with small adrenal glands thus far. In a 15-year follow-up, the patient's height was approximately average for females before age 4 and fell to - 1 SDS at 10 years of age. Her bone age was similar to her chronological age from age 4 to age 15 years. CONCLUSIONS In conclusion, this is a classic case of CLAH with exceptionally small adrenal glands. Q77X mutation seems to be more common in Chinese CLAH patients. Additionally, this is the first report of the growth pattern associated with CLAH after a 15-year follow-up.
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference.
Wen, W, Kato, N, Hwang, JY, Guo, X, Tabara, Y, Li, H, Dorajoo, R, Yang, X, Tsai, FJ, Li, S, et al
Scientific reports. 2016;:17958
Abstract
Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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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.
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Cardiovascular events in a prehypertensive Chinese population: four-year follow-up study.
Wu, S, Huang, Z, Yang, X, Li, S, Zhao, H, Ruan, C, Wu, Y, Xin, A, Li, K, Jin, C, et al
International journal of cardiology. 2013;(5):2196-9
Abstract
OBJECTIVES This study aimed to determine the occurrence of cardiovascular (CV) events in a prehypertensive Chinese population. METHODS Participants meeting the JNC 7 diagnostic criteria for prehypertension (n=30,027) and ideal blood pressure (n=15,614) were enrolled in this prospective, observational cohort. New CV events were collected during follow-up of 38-53 months (mean 47.58 ± 3.19 months). A multivariate Cox proportional hazard regression model was used to analyze factors influencing CV events. RESULTS Four hundred sixty-one CV events occurred during the follow-up period. Cumulative incidence rates for total CV events, cerebral infarct, cerebral hemorrhage, myocardial infarct, and deaths due to CV in the prehypertensive population were 1.19%, 0.57%, 0.20%, 0.23%, and 0.23%, respectively. These rates were higher than those of the ideal blood pressure group (0.67%, 0.27%, 0.12%, 0.17%, and 0.15% respectively). After correcting for traditional CV risk factors, relative risks (RRs) for total CV events, cerebral infarct and cerebral hemorrhages in the prehypertensive population were 1.32 (95% confidence intervals (CI): 1.06-1.65), 1.55 (95% CI: 1.10-2.18) and 1.40 (95% CI: 0.82-2.37) higher than those in the ideal blood pressure population. Compared to the ideal blood pressure group, the prehypertensive population was older, more likely male, and had higher triglycerides, total cholesterol, low-density lipoprotein cholesterol, and body mass index (p<0.05). CONCLUSION Prehypertension is an independent risk factor for total CV events and stroke.
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Mutational screening of 10 genes in Chinese patients with microphthalmia and/or coloboma.
Zhang, X, Li, S, Xiao, X, Jia, X, Wang, P, Shen, H, Guo, X, Zhang, Q
Molecular vision. 2009;:2911-8
Abstract
PURPOSE To screen ten genes for mutations in 32 Chinese patients with microphthalmia and/or coloboma. METHODS Genomic DNA was prepared from 32 unrelated patients with microphthalmia (nine probands) and uveal coloboma (23 probands). Cycle sequencing was used to detect sequence variations in ten genes, including BMP4, VSX2, CRYBA4, GDF6, OTX2, RAX, SIX3, SIX6, SOX2, and LRP6. Variations were further evaluated in 96 unrelated controls by using restriction fragment length polymorphism (RFLP) or heteroduplex-single strand conformation polymorphism (HA-SSCP) analysis. RESULTS In the ten genes, a novel c.751C>T (p.H251Y) in BMP4 was detected in a patient with bilateral microphthalmia and unilateral cataract. The c.751C>T variation is also present in his healthy brother (and possibly one of the normal parents). In addition, a novel c.608G>A (p.R203Q) in SIX6 was identified in an internal control for optimizing experimental conditions. The internal control was from a girl with typical aniridia and an identified c.718C>T (p.R240X) mutation in PAX6, suggesting the c.608G>A variation in SIX6 was unlikely to play a role in her ocular phenotype. The c.751C>T in BMP4 and the c.608G>A in SIX6 were not present in the 96 normal controls. In addition, 16 nucleotide substitutions, including eight known SNPs and eight new synonymous changes, were detected. CONCLUSIONS Although the genetic etiology for microphthalmia and/or coloboma is still elusive, rare variations in the related genes, such as c.608 G>A in SIX6 and c.751C>T in BMP4, may not be causative. These results further emphasize the importance of careful clinical and genetic analysis in making mutation-disease associations.