Morisada, Naoya, Rendtorff, Nanna Dahl, Nozu, Kandai, Morishita, Takahiro, Miyakawa, Takayuki, Matsumoto, Tohru, Hisano, Satoshi, Iijima, Kazumoto, Tranebjaerg, Lisbeth, Shirahata, Akira, Matsuo, Masafumi, and Kusuhara, Koichi
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-otorenal (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 ~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. Keywords BOR syndrome * EYA1 * Renal insufficiency * MLPA * LINE-1 (L1) * Retrotransposition * Insertion, Introduction Branchio-oto-renal (BOR) syndrome (OMIM 113650), which was first reported in 1975 by Melnick et al. [1], is characterized by branchiogenic malformation, deafness, and renal abnormalities. BOR syndrome is an [...]