Zhou J, Gregory M C, Hertz J M, Barker D F, Atkin C, Spencer E S, Tryggvason K
Biocenter and Department of Biochemistry, University of Oulu, Finland.
Kidney Int. 1993 Mar;43(3):722-9. doi: 10.1038/ki.1993.103.
We have screened 110 unrelated Alport syndrome kindreds for mutations in the exon 48 region of the COL4A5 collagen gene. Denaturing gradient gel electrophoresis (DGGE) of the PCR-amplified region of exon 48 revealed sequence variants in DNA from affected males and carriers of three unrelated kindreds. All three kindreds have classical Alport syndrome of the juvenile type. DNA-sequencing analyses demonstrated two different single base changes in the codon for arginine-1563 located in exon 48. In Utah kindred 2103, there was a substitution of C by T resulting in the change of the CGA codon for arginine to the translation stop codon TGA. In Utah kindred 2123 and in the Danish kindred A13, there was a C-->T mutation in the noncoding strand changing the same codon to CAA for glutamine. Both mutations were confirmed by allele-specific hybridization on PCR-amplified DNA from other family members.
我们对110个无亲缘关系的奥尔波特综合征家族进行了筛查，以寻找Ⅳ型胶原基因（COL4A5）第48外显子区域的突变。对第48外显子PCR扩增区域进行变性梯度凝胶电泳（DGGE）分析，发现来自3个无亲缘关系家族的患病男性和携带者的DNA存在序列变异。这3个家族均患有典型的青少年型奥尔波特综合征。DNA序列分析显示，位于第48外显子的精氨酸-1563密码子存在两种不同的单碱基变化。在犹他州家族2103中，发生了C被T取代的情况，导致精氨酸的CGA密码子变为翻译终止密码子TGA。在犹他州家族2123和丹麦家族A13中，非编码链发生了C→T突变，使同一密码子变为谷氨酰胺的CAA密码子。通过对其他家族成员PCR扩增的DNA进行等位基因特异性杂交，证实了这两种突变。
