Exp Dermatol. 2011 Jan;20(1):74-6. doi: 10.1111/j.1600-0625.2010.01177.x. Epub 2010 Oct 18.
Junctional epidermolysis bullosa associated with pyloric atresia (JEB-PA) is one of the most severe inherited skin diseases, characterized by generalized blister formation and occlusion of the pylorus at birth. Most JEB-PA patients have mutations in the gene encoding β4 integrin (ITGB4). No recurrent mutations in ITGB4 have been described as having founder effects. We collected three JEB-PA families with c.1938delC in ITGB4. Haplotype analysis using single nucleotide polymorphism markers throughout ITGB4 suggested one rare haplotype (2.8% of the Han Chinese and ethnic Japanese populations) in all alleles with c.1938delC. The parents of one of the three families sought prenatal diagnosis for a subsequent pregnancy. We succeeded in performing prenatal exclusion of JEB-PA using the foetal genomic DNA. Our study clearly demonstrated that recurrent c.1938delC in ITGB4 is a founder mutation in JEB-PA patients, and that genotyping of the mutation can be utilized for prenatal diagnosis of JEB-PA.
交界性大疱性表皮松解症伴幽门闭锁（JEB-PA）是最严重的遗传性皮肤疾病之一，其特征为出生时即出现全身性水疱形成和幽门闭锁。大多数 JEB-PA 患者的基因编码β4 整联蛋白（ITGB4）存在突变。尚无关于 ITGB4 中具有创始效应的复发性突变的报道。我们收集了三个 ITGB4 中存在 c.1938delC 的 JEB-PA 家系。对整个 ITGB4 中的单核苷酸多态性标记物进行单倍型分析表明，所有携带 c.1938delC 的等位基因中存在一种罕见的单倍型（汉族和日本人群中的 2.8%）。三个家系中的一个家系的父母为后续妊娠寻求产前诊断。我们成功地使用胎儿基因组 DNA 进行了 JEB-PA 的产前排除。我们的研究清楚地表明，ITGB4 中的复发性 c.1938delC 是 JEB-PA 患者的创始突变，对该突变进行基因分型可用于 JEB-PA 的产前诊断。
