Massive parallel sequencing as a new diagnostic approach for phenylketonuria and tetrahydrobiopterin-deficiency in Thailand.
Massive parallel sequencing as a new diagnostic approach for phenylketonuria and tetrahydrobiopterin-deficiency in Thailand.
复制标题
DOI：
10.1186/s12881-017-0464-x
复制
发表时间：
2017-09-16
影响因子：
--
通讯作者：
Shotelersuk V
中科院分区：
文献类型：
--
作者：
Chaiyasap P;Ittiwut C;Srichomthong C;Sangsin A;Suphapeetiporn K;Shotelersuk V
高苯丙氨酸血症（HPA）可分为由苯丙氨酸羟化酶（PAH）基因突变引起的苯丙酮尿症（PKU）和由参与四氢生物蝶呤（BH4）生物合成途径的基因改变引起的BH4缺乏症。限制苯丙氨酸的饮食被认为是 PKU 预防不可逆智力障碍的主要治疗方法。然而，同样的饮食干预对 BH4 缺乏症患者并不那么有效，因为 BH4 也是许多神经递质合成的辅助因子。我们利用下一代测序（NGS）技术对四名无关的泰国高苯丙氨酸血症患者进行了调查。我们成功鉴定了 PKU 或 BH4 缺陷相关基因中的所有 8 个突变等位基因，其中包括 3 个新突变，1 个是 PAH 突变，2 个是 PTS 突变，从而对这些患者做出了明确诊断。然后可以提供适当的管理。这项研究发现了 PAH 或 PTS 基因中的三个新突变，并支持使用 NGS 作为明确诊断高苯丙氨酸血症的替代分子遗传学方法，从而在泰国对这些患者进行适当的治疗。
Hyperphenylalaninemia (HPA) can be classified into phenylketonuria (PKU) which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, and BH4 deficiency caused by alterations in genes involved in tetrahydrobiopterin (BH4) biosynthesis pathway. Dietary restriction of phenylalanine is considered to be the main treatment of PKU to prevent irreversible intellectual disability. However, the same dietary intervention in BH4 deficiency patients is not as effective, as BH4 is also a cofactor in many neurotransmitter syntheses. We utilized next generation sequencing (NGS) technique to investigate four unrelated Thai patients with hyperphenylalaninemia. We successfully identified all eight mutant alleles in PKU or BH4-deficiency associated genes including three novel mutations, one in PAH and two in PTS, thus giving a definite diagnosis to these patients. Appropriate management can then be provided. This study identified three novel mutations in either the PAH or PTS gene and supported the use of NGS as an alternative molecular genetic approach for definite diagnosis of hyperphenylalaninemia, thus leading to proper management of these patients in Thailand.
登录
查看更多内容
DOI：
10.1038/nrg3493
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
5.3
作者：
Liu, TT;Hsiao, KJ
通讯作者：
Hsiao, KJ
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.
影响因子：
14.5
作者：
Clot, Fabienne;Grabli, David;Brice, Alexis
通讯作者：
Brice, Alexis