检测编号：NA0500004

基因 GCH1 与疾病

由于四氢生物喋呤（BH4）是苯基丙氨酸代谢过程中的辅助物质。BH4对于许多氨基酸的生成起关键作用，如将苯丙氨酸转化为酪氨酸；BH还参与一些神经递质的合成，如多巴胺和血清素，从而影响大脑对人体物理运动、情绪、情感和睡眠等的控制。GCH1,PCBD1,PTS,QDPR这几个基因指导合成和回收四氢生物喋呤的关键酶，这几个基因突变导致四氢生物喋呤缺乏，苯基丙氨酸在体内堆积从而对机体形成损害。

GCH1编码三磷酸鸟苷环水解酶1，该酶参与BH4生成反应的第一步。已发现140多种基因突变会导致多巴反应性肌张力障碍，表现为肌肉不随意收缩、颤动，可以通过服用左旋多巴胺来治疗；另外至少有7种突变会导致四氢蝶呤缺乏症，占比4%，苯丙氨酸无法转化为酪氨酸，有害产物堆积对机体造成毒性。

基因名称	基因全名	基因位置	外显子个数	CDS长度
GCH1	GTP cyclohydrolase 1	14q22.1-q22.2	6	约2925 bp
基因摘要	This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008].

基因 PCBD1 与疾病

由于四氢生物喋呤是苯基丙氨酸代谢过程中的辅助物质。GCH1,PCBD2,PTS,QDPR这几个基因指导合成和回收四氢生物喋呤的关键酶，这几个基因突变导致四氢生物喋呤缺乏，苯基丙氨酸在体内堆积从而对机体形成损害。

已发现至少9种基因突变会导致四氢蝶呤甲胺醇脱水酶缺乏，从而导致四氢蝶呤缺乏症，占比约5%；不过该基因突变影响不大，其他酶能弥补该酶活性降低

基因名称	基因全名	基因位置	外显子个数	CDS长度
PCBD1	pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 alpha	10q22	4	约1156 bp
基因摘要	This gene encodes a member of the pterin-4-alpha-carbinolamine dehydratase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The encoded protein functions as both a dehydratase involved in tetrahydrobiopterin biosynthesis, and as a cofactor for HNF1A-dependent transcription. A deficiency of this enzyme leads to hyperphenylalaninemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014].

基因 PTS 与疾病

由于四氢生物喋呤是苯基丙氨酸代谢过程中的辅助物质。GCH1,PCBD3,PTS,QDPR这几个基因指导合成和回收四氢生物喋呤的关键酶，这几个基因突变导致四氢生物喋呤缺乏，苯基丙氨酸在体内堆积从而对机体形成损害。

PTS基因编码四氢生物喋呤合成反应中第二步的关键酶PTS。已发现45种突变会导致四氢蝶呤缺乏症，占比50%以上。PTS缺乏使得苯丙氨酸无法代谢，有害物质堆积损害机体，尤其是脑损伤，从而引起智力残疾。

基因名称	基因全名	基因位置	外显子个数	CDS长度
PTS	6-pyruvoyltetrahydropterin synthase	11q22.3	6	约934 bp
基因摘要	The enzyme encoded by this gene catalyzes the elimination of inorganic triphosphate from dihydroneopterin triphosphate, which is the second and irreversible step in the biosynthesis of tetrahydrobiopterin from GTP. Tetrahydrobiopterin, also known as BH(4), is an essential cofactor and regulator of various enzyme activities, including enzymes involved in serotonin biosynthesis and NO synthase activity. Mutations in this gene result in hyperphenylalaninemia. [provided by RefSeq, Oct 2008].

基因 QDPR 与疾病

由于四氢生物喋呤是苯基丙氨酸代谢过程中的辅助物质。GCH1,PCBD4,PTS,QDPR这几个基因指导合成和回收四氢生物喋呤的关键酶，这几个基因突变导致四氢生物喋呤缺乏，苯基丙氨酸在体内堆积从而对机体形成损害。

QDPR编码醌式二氢蝶啶还原酶，该酶参与BH4的回收。该基因突变导致醌式二氢蝶啶还原酶缺乏，从而引起四氢蝶呤缺乏症，占比约三分之一。醌式二氢蝶啶还原酶活性降低使得一些神经传导物质产量降低，影响大脑功能，造成智力残疾。

基因名称	基因全名	基因位置	外显子个数	CDS长度
QDPR	quinoid dihydropteridine reductase	4p15.31	7	约1653 bp
基因摘要	This gene encodes the enzyme dihydropteridine reductase, which catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin. This enzyme is an essential component of the pterin-dependent aromatic amino acid hydroxylating systems. Mutations in this gene resulting in QDPR deficiency include aberrant splicing, amino acid substitutions, insertions, or premature terminations. Dihydropteridine reductase deficiency presents as atypical phenylketonuria due to insufficient production of biopterin, a cofactor for phenylalanine hydroxylase. [provided by RefSeq, Jul 2008].