title: Characterization of 28 novel patients expands the mutational and phenotypic spectrum of Lowe syndrome.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Twenty-eight novel patients with suspected Lowe syndrome were studied.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Recker
authors.forename: Marcin
authors.initials: M
authors.lastname: Zaniew
authors.forename: Detlef
authors.initials: D
authors.lastname: Böckenhauer
authors.forename: Nunzia
authors.initials: N
authors.lastname: Miglietti
authors.forename: Arend
authors.initials: A
authors.lastname: Bökenkamp
authors.forename: Anna
authors.initials: A
authors.lastname: Moczulska
authors.forename: Anna
authors.initials: A
authors.lastname: Rogowska-Kalisz
authors.forename: Guido
authors.initials: G
authors.lastname: Laube
authors.forename: Valerie
authors.initials: V
authors.lastname: Said-Conti
authors.forename: Belde
authors.initials: B
authors.lastname: Kasap-Demir
authors.forename: Anna
authors.initials: A
authors.lastname: Niemirska
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Litwin
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Siteń
authors.forename: Krystyna H
authors.initials: KH
authors.lastname: Chrzanowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: Sidharth K
authors.initials: SK
authors.lastname: Sethi
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
authors.forename: Franca
authors.initials: F
authors.lastname: Anglani
authors.forename: Maria
authors.initials: M
authors.lastname: Addis
authors.forename: Anna
authors.initials: A
authors.lastname: Wasilewska
authors.forename: Maria
authors.initials: M
authors.lastname: Szczepańska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Pawlaczyk
authors.forename: Przemysław
authors.initials: P
authors.lastname: Sikora
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D000293:Adolescent; D002386:Cataract / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D018899:CpG Islands; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006801:Humans; D012001:Hyperacusis / Q000175:diagnosis / Q000235:genetics; D007194:India / Q000453:epidemiology; D007223:Infant; D008297:Male; D009154:Mutation; D009800:Oculocerebrorenal Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011237:Predictive Value of Tests; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000235:genetics; D013921:Thrombocytopenia / Q000175:diagnosis / Q000235:genetics; D013997:Time Factors; D055815:Young Adult
chemical_list: D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human