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EYA1 and SIX1 gene mutations in Japanese patients with branchio-oto-renal (BOR) syndrome and related conditions

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Abstract

We isolated genomic DNA from 15 patients with branchio-oto-renal (BOR) syndrome or BOR-related conditions. Seven patients had BOR syndrome (two familial and five sporadic), and eight had deafness and renal malformations without branchial fistula (BOR-related conditions). We analyzed all exons and exon–intron boundaries of EYA1 and SIX1 using the polymerase chain reaction (PCR) direct sequencing, and characterized their mutations. In some patients, analysis of mRNA by reverse transcription (RT)-PCR was performed to examine whether the mutation affects the mRNA splicing. We identified five novel disease-causing heterozygous EYA1 mutations in five patients with BOR syndrome (two familial and three sporadic, 5/7=71%), but EYA1 and SIX1 mutations were not detected in the other two patients with BOR syndrome or any of the patients with BOR-related conditions. The detected EYA1 mutations were two nonsense mutations, two splicing acceptor-site mutations, and a point mutation (G>T) of the first base of exon 10. Analysis of mRNA by RT-PCR direct sequencing revealed that the latter point mutation led to the skipping of exon 10. In conclusion, (1) EYA1 mutations are a major cause of BOR syndrome in Japanese, (2) EYA1 and SIX1 mutations were not a major cause of BOR-related conditions, (3) we demonstrated for the first time that the point mutation (G>T) of the first base of the exon in EYA1 gene induced exon skipping.

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Acknowledgements

This study was supported by a Health and Labor Sciences Research Grant (H16-Kodomo-015 to Dr. Iijima) and a Grant for Child Health and Development (15C-1 to Dr. Okuyama).

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Authors and Affiliations

  1. Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, Tokyo, Japan

    Michiyo Okada & Torayuki Okuyama

  2. Department of Nephrology, National Children’s Medical Center, National Center for Child Health and Development, 10-1, Okura 2chome, Setagaya-ku, Tokyo, 157-8535, Japan

    Rika Fujimaru & Kazumoto Iijima

  3. Department of Otolaryngology and Communication Disorder, National Center for Child Health and Development, Tokyo, Japan

    Noriko Morimoto

  4. Division of Pediatric Nephrology and Metabolisms, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan

    Kenichi Satomura

  5. Department of Nephrology, Fukuoka Children’s Hospital, Fukuoka, Japan

    Yoshikazu Kaku

  6. Department of Pediatrics, Chukyo Hospital, Nagoya, Japan

    Kazuo Tsuzuki

  7. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

    Kandai Nozu

Authors
  1. Michiyo Okada
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  2. Rika Fujimaru
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  3. Noriko Morimoto
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  4. Kenichi Satomura
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  5. Yoshikazu Kaku
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  6. Kazuo Tsuzuki
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  7. Kandai Nozu
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  8. Torayuki Okuyama
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  9. Kazumoto Iijima
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Correspondence to Kazumoto Iijima.

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Okada, M., Fujimaru, R., Morimoto, N. et al. EYA1 and SIX1 gene mutations in Japanese patients with branchio-oto-renal (BOR) syndrome and related conditions. Pediatr Nephrol 21, 475–481 (2006). https://doi.org/10.1007/s00467-006-0041-6

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  • DOI: https://doi.org/10.1007/s00467-006-0041-6

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