Abstract
Molecular diagnosis makes a substantial contribution to precise diagnosis, subclassification, prognosis, and selection of therapy. Mutations in the PDS (SLC26A4) gene are known to be responsible for both Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct, and the molecular confirmation of the PDS gene has become important in the diagnosis of these conditions. In the present study, PDS mutation analysis confirmed that PDS mutations were present and significantly responsible in 90% of Pendred families, and in 78.1% of families with nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Furthermore, variable phenotypic expression by the same combination of mutations indicated that these two conditions are part of a continuous category of disease. Interestingly, the PDS mutation spectrum in Japanese, including the seven novel mutations revealed by this study, is very different from that found in Caucasians. Of the novel mutations detected, 53% were the H723R mutation, suggesting a possible founder effect. Ethnic background is therefore presumably important and should be noted when genetic testing is being performed. The PDS gene mutation spectrum in Japanese may be representative of those in Eastern Asian populations and its elucidation is expected to facilitate the molecular diagnosis of a variety of diseases.
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Acknowledgements
We thank all the subjects who participated in the present project. We also thank Dr Kyoko Nagai (Gunma University School of Medicine), Dr Satoshi Iwasaki (Hamamatsu University School of Medicine), Dr Tatsuo Matsunaga (International University of Health and Welfare), Drs Noriko Minami and Yumiko Hosoya (Iwate Medical University), Drs Hajime Ishinaga and Atsushi Yuta (Mie University), Dr Tetsuya Tono (Miyazaki Medical College), Dr Yukihiko Kanda (Nagasaki University School of Medicine), Dr Hitoshi Sato (Niigata University School of Medicine), Drs Tatsuhiko Harada and Ryuichi Osanai (Saitama Medical School), Drs Hitome Kobayashi and Yasuya Nomura (Showa University), and Dr Tatsuya Yamasoba (Tokyo University) for sending the samples of their patients. This work was supported by the Ministry of Health and Welfare, Japan (SU), and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (SU).
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Tsukamoto, K., Suzuki, H., Harada, D. et al. Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese. Eur J Hum Genet 11, 916–922 (2003). https://doi.org/10.1038/sj.ejhg.5201073
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DOI: https://doi.org/10.1038/sj.ejhg.5201073
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