Grandchamp B, Picat C, Kauppinen R, Mignotte V, Peltonen L, Mustajoki P, Roméo P H, Goossens M, Nordmann Y
Laboratoire de Génétique Moléculaire, Faculté de Médecine X Bichat, Paris, France.
Eur J Clin Invest. 1989 Oct;19(5):415-8. doi: 10.1111/j.1365-2362.1989.tb00252.x.
Porphobilinogen deaminase, the third enzyme of the haem biosynthetic pathway, is encoded by two distinct mRNA species expressed in a tissue-specific manner from a single gene. These two mRNAs are transcribed from two promoters and only differ in their first exon. An inherited deficiency or porphobilinogen deaminase in man is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. In the present report, we describe the molecular abnormality responsible for a variant form of acute intermittent porphyria where the enzyme defect is restricted to non-erythroid cells. Upon cloning and sequencing the mutant allele of a patient from a large Finnish kindred, a single-base substitution within the 5'-splice donor sequence of intron 1 was found at the last position of exon 1 (CG----CT). The identification of this mutation allowed us to detect asymptomatic gene carriers among family members using in vitro amplification of DNA and hybridization of the target sequence to allele-specific oligonucleotides.
胆色素原脱氨酶是血红素生物合成途径的第三种酶，由单一基因以组织特异性方式表达的两种不同mRNA编码。这两种mRNA从两个启动子转录而来，仅在其第一个外显子上有所不同。人类中胆色素原脱氨酶的遗传性缺陷导致常染色体显性疾病急性间歇性卟啉症。在蛋白质水平上已描述了不同类型的突变，表明这是一种异质性疾病。在本报告中，我们描述了一种急性间歇性卟啉症变异形式的分子异常，其中酶缺陷仅限于非红细胞。在克隆和测序来自一个大型芬兰家族的一名患者的突变等位基因后，发现在外显子1的最后位置（CG----CT），内含子1的5'-剪接供体序列内有一个单碱基取代。该突变的鉴定使我们能够通过DNA的体外扩增以及靶序列与等位基因特异性寡核苷酸的杂交来检测家族成员中的无症状基因携带者。
