ILLEGITIMATE TRANSCRIPTION OF THE PHENYLALANINE-HYDROXYLASE GENE IN LYMPHOCYTES FOR IDENTIFICATION OF MUTATIONS IN PHENYLKETONURIA
ILLEGITIMATE TRANSCRIPTION OF THE PHENYLALANINE-HYDROXYLASE GENE IN LYMPHOCYTES FOR IDENTIFICATION OF MUTATIONS IN PHENYLKETONURIA
复制标题
DOI：
10.1093/hmg/2.1.31
复制
发表时间：
1993-01-01
影响因子：
3.5
通讯作者：
REY, J
中科院分区：
文献类型：
--
作者：
ABADIE, V;JARUZELSKA, J;REY, J
利用苯丙氨酸羟化酶 (PAH) 基因的“非法”转录，我们能够分析高苯丙氨酸血症儿童循环淋巴细胞中的 PAH cDNA 序列。利用这种方法，我们还从两名患者的肝脏和淋巴细胞中鉴定出了 3 个新的 cDNA 突变。通过扩增片段的异常迁移模式检测到的一种突变是内含子 10 剪接受体位点中的 C 到 T 转变，导致外显子 11 的跳过，并导致外显子 12 (-3 IVS10) 下游的 RNA 翻译过早终止。另外两个突变是外显子 10 和 11 的错义突变（分别为 L333F 和 E390G）。本研究支持这样的观点，即循环淋巴细胞可以轻松获取 PAH 基因转录本，其核苷酸序列与肝脏中报道的相同，因此代表了苯丙酮尿症分子遗传学研究的有用工具。
Taking advantage of the 'illegitimate' transcription of the phenylalanine hydroxylase (PAH) gene, we have been able to analyse the PAH cDNA sequence of hyperphenylalaninemic children in circulating lymphocytes. Using this approach, we have also identified 3 novel mutations in cDNA from liver and lymphocytes of two patients. One mutation, detected by the abnormal pattern of migration of an amplified fragment, is a C to T transition in the splice acceptor site of intron 10, which resulted in the skipping of exon 11 with the premature termination of RNA translation downsteam from exon 12 (-3 IVS10). The other two mutations are missense mutations in exons 10 and 11 (respectively, L333F and E390G). The present study supports the view that circulating lymphocytes give easy access to PAH gene transcripts whose nucleotide sequence is identical to that reported in liver and therefore represent a useful tool for molecular genetic studies in phenylketonuria.