多重连接依赖探针扩增
医学
点突变
桑格测序
基因型
21羟化酶
表型
基因突变
复合杂合度
胃肠病学
儿科
先天性肾上腺增生
突变
新生儿筛查
内科学
基因型-表型区分
等位基因
基因
遗传学
生物
外显子
作者
R F Wang,Xiaochu Gu,J Ye,Lin Han,Wei Liu,H W Zhang,Yongguo Yu,Zhicheng Gong
出处
期刊:PubMed
日期:2016-09-01
卷期号:54 (9): 679-85
被引量:2
标识
DOI:10.3760/cma.j.issn.0578-1310.2016.09.010
摘要
To analyze the phenotype-genotype correlation of 21-hydroxylase deficiency (21-OHD) patients found by neonatal screening, and to investigate the characteristics of gene frequency of these patients.Clinical and biochemical data of 66 21-OHD patients diagnosed by neonatal screening in department of pediatric endocrinology and genetics and neonatal screening center of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from 2009 to 2014 were retrospectively analyzed. Point mutations of CYP21A2 gene were analyzed by Sanger sequencing, and large gene deletions were detected by multiplex ligation-dependent probe amplification (MLPA). Then the correlation between phenotypes and genotypes of these patients were analyzed.(1) Forty-one out of 66 patients who presented adrenal crisis or other signs of salt loss at age range from 4 days to 2 months were classified as salt-wasting forms. The remaining 25 patients did not present any signs of salt loss at preliminary diagnosis (12 days-2 months). (2) Definite mutations of CYP21A2 gene on two alleles were found in all 66 patients (132 alleles). A total of thirteen types of different point mutations (98/132, 74.2%), large gene deletions (24/132, 18.2%) and clusters of point mutations (10/132, 7.6%) were found. The most frequent point mutations were I2G, p. I173N, p. R357W, p. G111Vfs*21 and p. Q319*, accounting for 65.2% of alleles. (3) Phenotype and genotype correlation analysis was performed in 41 21-OHD patients with salt wasting forms. Predicted phenotypes according to genotypes in 36 (87.8%) of the 41 patients were consistent with their actual phenotypes. In 4 out of the 41 patients, the actual phenotypes were different from predicted phenotypes according to their genotypes. And in one patient, prediction of phenotype could not be made based on genotype as carrying an unknown function mutation on one allele.Adrenal crisis or other signs of salt loss were found in 62% of 21-OHD patients at age range from 4 days to 2 months. In 66 Chinese 21-OHD children, total mutation frequency of I2G, p. I173N, p. R357W, p. G111Vfs*21 and p. Q319* accounted for 65.2% of alleles. In 87.8% of patients with salt wasting forms, predicted phenotypes according to genotypes were consistent with their actual phenotypes.
科研通智能强力驱动
Strongly Powered by AbleSci AI