Noji Yoshihiro, Inazu Akihiro, Higashikata Toshinori, Nohara Atsushi, Kawashiri Masa-aki, Yu Wenxin, Todo Yasuhiro, Nozue Tsuyoshi, Uno Yoshihide, Hifumi Senshu, Mabuchi Hiroshi
Molecular Genetics of Cardiovascular Disorders, Division of Cardiovascular Medicine (The Second Department of Internal Medicine), Graduate School of Medical Science, Kanazawa University, Kanazawa.
Intern Med. 2004 Dec;43(12):1171-6. doi: 10.2169/internalmedicine.43.1171.
Pseudoxanthoma elasticum (PXE) is a rare, inherited, systemic disease of elastic tissue that in particular affects the skin, eyes, and cardiovascular system. Recently, the ABCC6 (MRP6) gene was found to cause PXE. A defective type of ABCC6 gene (16pl3.1) was determined in two Japanese patients with PXE. In order to determine whether these patients have a defect in ABCC6 gene, we examined each of 31 exons and flanking intron sequences by PCR methods (SSCP screening and direct sequencing). We found two novel missense variants in exon 26 and 29 in a compound heterozygous state in the first patient. One is a missense mutation (c.3661C>T; p.R1221C) in exon 26 and the other is a missense mutation (c.4069C>T; p.R1357W) in exon 29. These mutations have not been detected in our control panel of 200 alleles. To our knowledge, this is the first report of mutation identification in the ABCC6 gene in Japanese PXE patients. The second patient was homozygous for 2542_2543delG in ABCC6 gene and heterozygous for 6 kb deletion of LDL-R gene. This case is the first report of a genetically confirmed case of double mutations both in PXE and FH loci.
弹性假黄瘤（PXE）是一种罕见的、遗传性的弹性组织全身性疾病，尤其会影响皮肤、眼睛和心血管系统。最近，发现ABCC6（MRP6）基因会导致PXE。在两名日本PXE患者中确定了一种有缺陷的ABCC6基因类型（16pl3.1）。为了确定这些患者的ABCC6基因是否存在缺陷，我们通过PCR方法（SSCP筛查和直接测序）检查了31个外显子和侧翼内含子序列中的每一个。我们在第一名患者中发现外显子26和29中存在两个新的错义变体，呈复合杂合状态。一个是外显子26中的错义突变（c.3661C>T；p.R1221C），另一个是外显子29中的错义突变（c.4069C>T；p.R1357W）。在我们的200个等位基因对照组中未检测到这些突变。据我们所知，这是日本PXE患者中ABCC6基因突变鉴定的首次报告。第二名患者ABCC6基因的2542_2543delG为纯合子，低密度脂蛋白受体（LDL-R）基因的6 kb缺失为杂合子。该病例是PXE和家族性高胆固醇血症（FH）位点双突变的基因确诊病例的首次报告。
