Abstract
Creatine transporter deficiency is an X-linked mental retardation disorder caused by mutations in the creatine transporter gene, SLC6A8. In a European Mental Retardation Consortium panel of 66 patients, we identified a male with mental retardation, caused by a c.1059_1061delCTT; p.Phe354del mutation in the SLC6A8 gene. With the use of direct DNA sequencing, the mutation was also found in the brother of the proband, but not in their mother. However, by analyzing EDTA blood of the mother with denaturing high-performance liquid chromatography (DHPLC), we could show that the mother displays low-level somatic mosaicism for the three base-pair deletion. This study indicates DHPLC as an important tool in the detection of low-level mosaicism, as does it illustrate the importance of considering somatic and germline mosaicism in the case of apparent de novo mutation.
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Acknowledgments
We thank Patricia S Darmin for her assistance with DHPLC optimization and Lorna Landegge-Pope, Donald E and Karin L Brass for their excellent reviewing. The work of Ofir T Betsalel, Cristina Martínez-Muñoz, Efraim H. Rosenberg, and Gajja S Salomons is supported by the Dutch society for Scientific Research (ZonMW/NWO), VIDI grant number 917.56.349, and that of Arjan PM de Brouwer and Ben CJ Hamel by the European Union grant QLG3-CT-2002-01819 EURO-MRX.
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Betsalel, O.T., van de Kamp, J.M., Martínez-Muñoz, C. et al. Detection of low-level somatic and germline mosaicism by denaturing high-performance liquid chromatography in a EURO-MRX family with SLC6A8 deficiency. Neurogenetics 9, 183–190 (2008). https://doi.org/10.1007/s10048-008-0125-5
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DOI: https://doi.org/10.1007/s10048-008-0125-5