Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China.
Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China.
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中国北方汉族苯丙酮尿症患者的 PAH 基因变异谱。
DOI：
10.1186/s12881-017-0467-7
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发表时间：
2017-10-05
影响因子：
--
通讯作者：
Kong X
中科院分区：
文献类型：
--
作者：
Liu N;Huang Q;Li Q;Zhao D;Li X;Cui L;Bai Y;Feng Y;Kong X
苯丙酮尿症（PKU）主要由苯丙氨酸羟化酶（PAH）缺乏引起，是一种最常见的遗传性代谢错误，会损害出生后的认知发育。各种多环芳烃变异的发病率因种族和民族而异。本研究的目的是表征中国北方汉族人群的多环芳烃基因变异。本研究共招募了655名PKU患者及其家属；每个先证者均经临床和生化诊断为苯丙酮尿症。通过直接Sanger测序和多重连接依赖探针扩增（MLPA）对受试者进行PAH单碱基变异和外显子缺失或重复的顺序筛选。鉴定出174种不同的多环芳烃变异谱：152种先前记录的变异和22种新变异。虽然单碱基变异分布在13个外显子中，但它们特别集中在外显子7（33.3%）、11（14.2%）、6（13.2%）、12（11.0%）、3（10.4%）和5（4.4%）。主要的变体是p.Arg243Gln(17.7%),其次是ex6 - 96 > G(8.3%)、p.Val399 =(6.4%)、p.Arg53His(4.7%)、p.Tyr356 *(4.7%)、p.Arg241Cys(4.6%)、p.Arg413Pro(4.6%)、p.Arg111 *(4.4%),和c.442-1G >(3.4%)。值得注意的是，两名患者也被确定为携带新生变异。中国北方汉族人群的多环芳烃基因变异组成与其他民族不同。因此，构建中国北方地区多环芳烃基因变异数据库，为基因诊断、产前诊断和人群筛查奠定基础。本文的在线版本（10.1186/s12881-017-0467-7）包含补充材料，仅供授权用户使用。
Phenylketonuria (PKU), which primarily results from a deficiency of phenylalanine hydroxylase (PAH), is one of the most common inherited inborn errors of metabolism that impairs postnatal cognitive development. The incidence of various PAH variations differs by race and ethnicity. The aim of the present study was to characterize the PAH gene variants of a Han population from Northern China. In total, 655 PKU patients and their families were recruited for this study; each proband was diagnosed both clinically and biochemically with phenylketonuria. Subjects were sequentially screened for single-base variants and exon deletions or duplications within PAH via direct Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). A spectrum of 174 distinct PAH variants was identified: 152 previously documented variants and 22 novel variants. While single-base variants were distributed throughout the 13 exons, they were particularly concentrated in exons 7 (33.3%), 11 (14.2%), 6 (13.2%), 12 (11.0%), 3 (10.4%), and 5 (4.4%). The predominant variant was p.Arg243Gln (17.7%), followed by Ex6-96A > G (8.3%), p.Val399 = (6.4%), p.Arg53His (4.7%), p.Tyr356* (4.7%), p.Arg241Cys (4.6%), p.Arg413Pro (4.6%), p.Arg111* (4.4%), and c.442-1G > A (3.4%). Notably, two patients were also identified as carrying de novo variants. The composition of PAH gene variants in this Han population from Northern China was distinct from those of other ethnic groups. As such, the construction of a PAH gene variant database for Northern China is necessary to lay a foundation for genetic-based diagnoses, prenatal diagnoses, and population screening. The online version of this article (10.1186/s12881-017-0467-7) contains supplementary material, which is available to authorized users.
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影响因子：
9.8
作者：
Anikster, Yair;Haack, Tobias B.;Schiff, Manuel
通讯作者：
Schiff, Manuel
中国汉族人群苯丙酮尿症突变谱：对常见突变地理分布的新见解
影响因子：
3.6
作者：
Zhu, Tianwen;Qin, Shengying;Gu, Xuefan
通讯作者：
Gu, Xuefan
影响因子：
3.8
作者：
Dobrowolski, Steven F.;Heintz, Caroline;Blau, Nenad
通讯作者：
Blau, Nenad
DOI：
10.3760/cma.j.issn.1003-9406.2011.04.007
发表时间：
2011-08-10
期刊：
Zhonghua Yixue Yichuanxue Zazhi
影响因子：
--
作者：
Gao Wei-hua;Zhang Quan-bin;Zhou Yong-an
通讯作者：
Zhou Yong-an
影响因子：
5.2
作者：
Trujillano, Daniel;Perez, Belen;Estivill, Xavier
通讯作者：
Estivill, Xavier