title: Molecular analysis of the XLRS1 gene in 4 females affected with X-linked juvenile retinoschisis.
abstract: BACKGROUND
  X-linked juvenile retinoschisis (XLRS) is the most common cause of juvenile macular degeneration in males. Because of its X-linked mode of transmission, the disease is rare in females. In this article, we describe a mutation screen conducted on a family in which 4 female patients affected with XLRS presented with an unusually severe phenotype.
  
  
  METHODS
  DNA was extracted from peripheral blood, and the XLRS1 gene was amplified on DNA samples of all the available family members. The mutation screen was conducted by performing direct DNA sequencing using an MJ Research PTC-225 Peltier Thermal Cycler.
  
  
  RESULTS
  A novel mutation, 588-593ins.C, was identified in exon 6 of the gene. The affected father was found to be heterozygous for the mutation, whereas all the female patients were homozygous for this mutation. The homozygosity of the mutation in the affected females led to severe phenotypes. The defective allele was expressed in infancy in 1 patient, whereas the disease manifested itself at variable ages in the other patients, reflecting a variation in the phenotype.
  
  
  CONCLUSIONS
  This report describes a novel mutation in a family in which consanguinity has led to XLRS in 4 females. A variation in the phenotype of the disease is consistent with the published literature and suggests the involvement of genetic modifiers or environmental factors in influencing the clinical severity of the disease.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan. ds436@medschl.cam.ac.uk
authors.forename: Danish
authors.initials: D
authors.lastname: Saleheen
authors.forename: Azam
authors.initials: A
authors.lastname: Ali
authors.forename: Shaheen
authors.initials: S
authors.lastname: Khanum
authors.forename: Mohammad Z
authors.initials: MZ
authors.lastname: Ozair
authors.forename: Moazzam
authors.initials: M
authors.lastname: Zaidi
authors.forename: Muhammad J
authors.initials: MJ
authors.lastname: Sethi
authors.forename: Nadir
authors.initials: N
authors.lastname: Khan
authors.forename: Philippe
authors.initials: P
authors.lastname: Frossard
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006801:Humans; D017075:Laser Coagulation; D008967:Molecular Biology; D008969:Molecular Sequence Data; D010375:Pedigree; D041441:Retinoschisis / Q000235:genetics* / Q000601:surgery
chemical_list: D005136:Eye Proteins; C108726:RS1 protein, human