Branchio-oto-renal syndrome caused by partial EYA1 deletion due to LINE-1 insertion.
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.
Department of Pediatrics, Saiseikai Yahata General Hospital, 5-9-27, Haruno-machi, Yahatahigashi-ku, Kitakyushu, Fukuoka, 805-0050, Japan. nmorisad7599@yahoo.co.jp
Naoya
N
Morisada
Nanna Dahl
ND
Rendtorff
Kandai
K
Nozu
Takahiro
T
Morishita
Takayuki
T
Miyakawa
Tohru
T
Matsumoto
Satoshi
S
Hisano
Kazumoto
K
Iijima
Lisbeth
L
Tranebjaerg
Akira
A
Shirahata
Masafumi
M
Matsuo
Koichi
K
Kusuhara
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001934:Branchial Region / Q000002:abnormalities*; D002648:Child; D004423:Ear / Q000002:abnormalities*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007668:Kidney / Q000002:abnormalities*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051437:Renal Insufficiency / Q000235:genetics; D013577:Syndrome
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases