Department of Pediatrics, Saiseikai Yahata General Hospital, 5-9-27, Haruno-machi, Yahatahigashi-ku, Kitakyushu, Fukuoka, 805-0050, Japan.
Pediatr Nephrol. 2010 Jul;25(7):1343-8. doi: 10.1007/s00467-010-1445-x. Epub 2010 Feb 4.
A 7-year-old Japanese girl with conductive deafness and preauricular fistulae developed proteinuria. She had renal insufficiency, and ultrasound revealed bilateral small kidneys. These findings indicated that she had branchio-oto-renal (BOR) syndrome. In the present patient, we identified, by using multiplex ligation-dependent probe amplification (MLPA) analysis, a heterozygous EYA1 gene deletion comprising at least exons 5 to 7. In her parents, we did not detect any deletion in EYA1 by MLPA, so the deletion was a de novo mutation. PCR analysis and sequencing of patient DNA revealed a heterozygous approximately 17 kb EYA1 deletion starting from the eight last bases of exon 4 and proceeding to base 1,217 of intron 7. Furthermore, in place of this deleted region was inserted a 3756-bp-long interspersed nuclear elements-1 (LINE-1, L1). Accordingly, RT-PCR showed that exons 4-7 were not present in EYA1 mRNA expressed from the mutated allele. Although there are reports of L1 element insertion occurring in various human diseases, this is the first report of a large EYA1 deletion in combination with L1 element insertion.
一位 7 岁的日本女孩患有传导性耳聋和耳前瘘管，并出现蛋白尿。她患有肾功能不全，超声显示双侧小肾脏。这些发现表明她患有鳃-耳-肾（BOR）综合征。在本患者中，我们通过多重连接依赖性探针扩增（MLPA）分析鉴定出 EYA1 基因的杂合缺失，至少包含外显子 5 至 7。在其父母中，我们通过 MLPA 未检测到 EYA1 缺失，因此该缺失是从头突变。对患者 DNA 的 PCR 分析和测序显示，EYA1 从外显子 4 的最后 8 个碱基开始，到内含子 7 的第 1217 位发生了一个约 17kb 的杂合缺失。此外，缺失区域插入了一个 3756bp 的长散布核元件-1（LINE-1，L1）。因此，RT-PCR 显示，从突变等位基因表达的 EYA1 mRNA 中不存在外显子 4-7。尽管有报道称 L1 元件插入发生在各种人类疾病中，但这是首次报道 EYA1 大片段缺失与 L1 元件插入相结合。
