title: Identification of Mutations in the PRDM5 Gene in Brittle Cornea Syndrome.
abstract: BACKGROUND
  Brittle cornea syndrome (BCS) is a rare autosomal recessive connective tissue disease characterized by variable combinations of corneal thinning and fragility, corneal ruptures either spontaneously or after minor trauma, blue sclerae, keratoconus, keratoglobus, and high myopia. So far, mutations in 2 genes, PRDM5 and ZNF469, have been associated with BCS. The purpose of this study is to describe novel mutations in the PRDM5 gene in patients with BCS.
  
  
  RESULTS
  Using homozygosity mapping with single-nucleotide polymorphism markers followed by whole-exome sequencing, we identified a novel homozygous splice site variant (c.93+5G>A) in the PRDM5 gene in a consanguineous Pakistani family with 4 affected individuals. Reverse transcription-polymerase chain reaction analysis from lymphocyte-derived RNA failed to reveal any exon skipping because of this splice site variant. A homozygous variant (c.11T>G; p.Gln4Pro) in SEC24D also segregated with the disease in this particular family. One previously known mutation (c.974del; p.Cys325LeufsX2) was identified in a sporadic patient with BCS from Serbia.
  
  
  CONCLUSIONS
  The current study revealed a novel mutation in the PRDM5 gene in a BCS family and recurrent mutation in a sporadic BCS patient. A variant in the SEC24D gene also segregated in the BCS family, although its role in the disease remains unclear.
authors.affiliation: Departments of *Ophthalmology; †Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands; ‡Al-Shifa Eye Trust Hospital, Rawalpindi, Pakistan; §Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan; ¶Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan; ‖Department of Ophthalmology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium; and **Center for Medical Genetics, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
authors.forename: Shazia
authors.initials: S
authors.lastname: Micheal
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.forename: Farrah
authors.initials: F
authors.lastname: Islam
authors.forename: Farah
authors.initials: F
authors.lastname: Akhtar
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Tassignon
authors.forename: Bart
authors.initials: B
authors.lastname: Loeys
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003241:Consanguinity; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007593:Joint Instability / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012868:Skin Abnormalities / Q000175:diagnosis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C487762:PRDM5 protein, human; D014157:Transcription Factors