Henriksson M, Timonen K, Mustajoki P, Pihlaja H, Tenhunen R, Peltonen L, Kauppinen R
Department of Medicine, University of Helsinki, Finland.
J Invest Dermatol. 1996 Feb;106(2):346-50. doi: 10.1111/1523-1747.ep12343020.
A novel mutation was identified by direct sequencing of genomic polymerase chain reaction products in each of four Finnish erythropoietic protoporphyria families. All four mutations, including two deletions (751delGAGAA and the first de novo mutation, 1122delT) and two point mutations (286C-->T and 343C-->T), resulted in a dramatically decreased steady-state level of the allelic transcript, since none of the mutations could be demonstrated by direct sequencing of the amplified cDNAs synthesized from total RNA extracted from patients' lymphoblast cell lines. Because the assays of the ferrochelatase activity and erythrocyte protoporphyrin identify asymptomatic patients poorly, the DNA-based demonstration of a mutation is the only reliable way to screen individuals for the disease-associated mutation.
通过对四个芬兰红细胞生成性原卟啉症家族中每个家族的基因组聚合酶链反应产物进行直接测序，鉴定出一种新的突变。所有四个突变，包括两个缺失突变（751delGAGAA和第一个新生突变1122delT）和两个点突变（286C→T和343C→T），均导致等位基因转录本的稳态水平显著降低，因为从患者淋巴母细胞系提取的总RNA合成的扩增cDNA进行直接测序无法证明这些突变。由于铁螯合酶活性和红细胞原卟啉检测对无症状患者的识别能力较差，基于DNA的突变证明是筛查个体是否存在疾病相关突变的唯一可靠方法。
