Human Genetics

, Volume 129, Issue 5, pp 513–519 | Cite as

Maternal de novo triple mosaicism for two single OCRL nucleotide substitutions (c.1736A>T, c.1736A>G) in a Lowe syndrome family

  • Markus Draaken
  • Carmen A. Giesen
  • Anne L. Kesselheim
  • Ronald Jabs
  • Stefan Aretz
  • Monika Kugaudo
  • Krystyna H. Chrzanowska
  • Malgorzata Krajewska-Walasek
  • Michael LudwigEmail author
Original Investigation


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.


Mutant Allele Spinal Muscular Atrophy Chronic Granulomatous Disease Inner Cell Mass Congenital Cataract 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank the family for their participation in this study and Pia Uerdingen, Bärbel Lippke, Maria Schubert and Dietlinde Stienen for laboratory technical assistance.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Markus Draaken
    • 1
    • 2
  • Carmen A. Giesen
    • 3
  • Anne L. Kesselheim
    • 3
  • Ronald Jabs
    • 4
  • Stefan Aretz
    • 1
  • Monika Kugaudo
    • 5
  • Krystyna H. Chrzanowska
    • 5
  • Malgorzata Krajewska-Walasek
    • 5
  • Michael Ludwig
    • 3
    Email author
  1. 1.Institute of Human GeneticsUniversity of BonnBonnGermany
  2. 2.Department of Genomics, Life and Brain CenterUniversity of BonnBonnGermany
  3. 3.Department of Clinical Chemistry and Clinical PharmacologyUniversity of BonnBonnGermany
  4. 4.Institute of Cellular NeurosciencesUniversity of BonnBonnGermany
  5. 5.Department of Medical GeneticsChildren’s Memorial Health InstituteWarsawPoland

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