caa a22 4500 445861789 CHVBK 20180317145445.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s00439-010-0944-y doi (NATIONALLICENCE)springer-10.1007/s00439-010-0944-y Maternal de novo triple mosaicism for two single OCRL nucleotide substitutions (c.1736A>T, c.1736A>G) in a Lowe syndrome family [Elektronische Daten] [Markus Draaken, Carmen Giesen, Anne Kesselheim, Ronald Jabs, Stefan Aretz, Monika Kugaudo, Krystyna Chrzanowska, Malgorzata Krajewska-Walasek, Michael Ludwig] Since the identification of the Lowe's oculocerebrorenal syndrome gene, more than 100 distinct OCRL mutations have been observed. Germline mosaicism has rarely been detected in Lowe families; however, the presence of mosaic mutations, in particular triple mosaicism, may often remain undiagnosed. In the course of OCRL analysis in a Polish family, the index case showed a hemizygous nucleotide transition (c.1736A>G, p.His507Arg). Gene analysis in the patient's mother not only provided evidence that she is a carrier of the mutant allele transmitted to her son but also showed an additional c.1736A>T (p.His507Leu) transversion affecting the same base position. DNA from a mouthwash sample from the mother showed a similar fluorescence intensity pattern at the affected nucleotide. These data, together with the findings that maternal grandparents solely showed wildtype sequence, implied a de novo mosaicism in the mother. Triple X syndrome was ruled out by karyotype analysis and a partial or complete gene duplication could be excluded. Allele-specific amplification confirmed the results of three alleles being present in the mother. The amount of wildtype allele detected in qPCR implied the presence of cells solely harboring c.1736A and single-cell PCR experiments confirmed the presence of non-mutant cells in the mother's blood. These data suggest that the mutations observed are the result of two de novo events in early embryogenesis of the mother. To the best of our knowledge, this is the first observation of triple mosaicism at a single nucleotide. Springer-Verlag, 2011 Draaken Markus Institute of Human Genetics, University of Bonn, Bonn, Germany aut Giesen Carmen Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany aut Kesselheim Anne Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany aut Jabs Ronald Institute of Cellular Neurosciences, University of Bonn, Bonn, Germany aut Aretz Stefan Institute of Human Genetics, University of Bonn, Bonn, Germany aut Kugaudo Monika Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland aut Chrzanowska Krystyna Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland aut Krajewska-Walasek Malgorzata Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland aut Ludwig Michael Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany aut Human Genetics Springer-Verlag 129/5(2011-05-01), 513-519 0340-6717 129:5<513 2011 129 439 https://doi.org/10.1007/s00439-010-0944-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0944-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Draaken Markus Institute of Human Genetics, University of Bonn, Bonn, Germany aut NATIONALLICENCE 700 1- Giesen Carmen Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany aut NATIONALLICENCE 700 1- Kesselheim Anne Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany aut NATIONALLICENCE 700 1- Jabs Ronald Institute of Cellular Neurosciences, University of Bonn, Bonn, Germany aut NATIONALLICENCE 700 1- Aretz Stefan Institute of Human Genetics, University of Bonn, Bonn, Germany aut NATIONALLICENCE 700 1- Kugaudo Monika Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland aut NATIONALLICENCE 700 1- Chrzanowska Krystyna Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland aut NATIONALLICENCE 700 1- Krajewska-Walasek Malgorzata Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland aut NATIONALLICENCE 700 1- Ludwig Michael Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/5(2011-05-01), 513-519 0340-6717 129:5<513 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer