Pediatric Nephrology

, Volume 30, Issue 6, pp 931–943 | Cite as

Characterization of 28 novel patients expands the mutational and phenotypic spectrum of Lowe syndrome

  • Florian Recker
  • Marcin Zaniew
  • Detlef Böckenhauer
  • Nunzia Miglietti
  • Arend Bökenkamp
  • Anna Moczulska
  • Anna Rogowska-Kalisz
  • Guido Laube
  • Valerie Said-Conti
  • Belde Kasap-Demir
  • Anna Niemirska
  • Mieczysław Litwin
  • Grzegorz Siteń
  • Krystyna H. Chrzanowska
  • Małgorzata Krajewska-Walasek
  • Sidharth K. Sethi
  • Velibor Tasic
  • Franca Anglani
  • Maria Addis
  • Anna Wasilewska
  • Maria Szczepańska
  • Krzysztof Pawlaczyk
  • Przemysław Sikora
  • Michael Ludwig
Original Article



The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked multi-systemic disorder, almost always characterized by the triad of congenital cataract, cognitive and behavioral impairment and a proximal tubulopathy.


Twenty-eight novel patients with suspected Lowe syndrome were studied.


All patients carried OCRL gene defects with mutational hot spots at CpG dinucleotides. Mutations previously unknown in Lowe syndrome were observed in ten of the 28 patients, and carriership was identified in 30.4 % of the mothers investigated. Mapping the exact breakpoints of a complete OCRL gene deletion revealed involvement of several flanking repeat elements. We noted a similar pattern of documented clinically relevant symptoms, and even though the patient cohort comprised relatively young patients, 32 % of these patients already showed advanced chronic kidney disease. Thrombocytopenia was seen in several patients, and hyperosmia and/or hyperacusis were reported recurrently. A p.Asp523Asn mutation in a Polish patient, associated with the typical cerebrorenal spectrum but with late cataract (10 year), was also evident in two milder affected Italian brothers with ocular involvement of similar progression.


We have identified clinical features in 28 patients with suspected Lowe syndrome that had not been recognized in Lowe syndrome prior to our study. We also provide further evidence that OCRL mutations cause a phenotypic continuum with selective and/or time-dependent organ involvement. At least some of these mutants might exhibit a genotype–phenotype correlation.


Oculocerebrorenal syndrome of Lowe OCRL Cataract CpG dinucleotides Hyperosmia Hyperacusis Thrombocytopenia 



We are grateful to the patients and their parents for their invaluable contributions. We thank Dr. Andrzej Blumczyński for his help with patient recruitment. We would also like to thank Hartmut Engels for performing array analysis and Pia Uerdingen and Markus Draaken for excellent technical assistance. Funding for this study was provided by the European Union, FP7 (grant agreement 2012-305608 “European Consortium for High-Throughput Research in Rare Kidney Diseases (EURenOmics)” to DB.


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Copyright information

© IPNA 2014

Authors and Affiliations

  • Florian Recker
    • 1
  • Marcin Zaniew
    • 2
  • Detlef Böckenhauer
    • 3
  • Nunzia Miglietti
    • 4
  • Arend Bökenkamp
    • 5
  • Anna Moczulska
    • 6
  • Anna Rogowska-Kalisz
    • 7
  • Guido Laube
    • 8
  • Valerie Said-Conti
    • 9
  • Belde Kasap-Demir
    • 10
  • Anna Niemirska
    • 11
  • Mieczysław Litwin
    • 11
  • Grzegorz Siteń
    • 12
  • Krystyna H. Chrzanowska
    • 13
  • Małgorzata Krajewska-Walasek
    • 13
  • Sidharth K. Sethi
    • 14
  • Velibor Tasic
    • 15
  • Franca Anglani
    • 16
  • Maria Addis
    • 17
  • Anna Wasilewska
    • 18
  • Maria Szczepańska
    • 19
  • Krzysztof Pawlaczyk
    • 20
  • Przemysław Sikora
    • 21
  • Michael Ludwig
    • 1
  1. 1.Department of Clinical Chemistry and Clinical PharmacologyUniversity of BonnBonnGermany
  2. 2.Children’s HospitalPoznańPoland
  3. 3.Institute of Child Health and Great Ormond Street Hospital for Children, National Health Service TrustUniversity College LondonLondonUK
  4. 4.Department of PediatricsUniversity of BresciaBresciaItaly
  5. 5.Department of PediatricsVU University Medical CenterAmsterdamThe Netherlands
  6. 6.Department of Pediatric NephrologyUniversity Children’s Hospital of CracowCracowPoland
  7. 7.Nephrology Division, Department of Pediatrics and ImmunologyPolish Mothers Memorial Hospital Research InstituteLodzPoland
  8. 8.Department of Pediatric NephrologyChildren’s Hospital ZürichZurichSwitzerland
  9. 9.Mater Dei HospitalMsidaMalta
  10. 10.Clinics of PediatricsTepecik Training and Research HospitalIzmirTurkey
  11. 11.Department of Nephrology and Kidney TransplantationThe Children’s Memorial Health InstituteWarsawPoland
  12. 12.Dialysis CenterDistrict HospitalRzeszowPoland
  13. 13.Department of Medical GeneticsThe Children’s Memorial Health InstituteWarsawPoland
  14. 14.Department of Pediatric Nephrology, The Medicity Hospital GurgaonKidney and Urology Institute MedantaGurgaonIndia
  15. 15.Department of Pediatric NephrologyUniversity Children’s HospitalSkopjeMacedonia
  16. 16.Laboratory of Histomorphology and Molecular Biology of the Kidney, Department of MedicineUniversity of PadovaPadovaItaly
  17. 17.Department of Public Health, Clinical and Molecular MedicineUniversity of CagliariCagliariItaly
  18. 18.Department of Pediatrics and NephrologyMedical University of BiałystokBiałystokPoland
  19. 19.Dialysis Division for Children, Department and Clinics of PediatricsMedical University of Silesia in KatowiceZabrzePoland
  20. 20.Department of Nephrology, Transplantology and Internal MedicinePoznań University of Medical SciencesPoznańPoland
  21. 21.Department of Pediatric NephrologyMedical University of LublinLublinPoland

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