title: Early-Onset X-Linked Retinitis Pigmentosa in a Heterozygous Female Harboring an Intronic Donor Splice Site Mutation in the Retinitis Pigmentosa GTPase Regulator Gene.
abstract: OBJECTIVE
  To report a heterozygous female presenting with an early-onset and severe form of X-linked retinitis pigmentosa (XLRP).
  
  
  METHODS
  This is a case series presenting the clinical findings in a heterozygous female with XLRP and two of her family members. Fundus photography, fundus autofluorescence, ocular coherence tomography, and visual perimetry are presented.
  
  
  RESULTS
  The proband reported here is a heterozygous female who presented at the age of 8 years with an early onset and aggressive form of XLRP. The patient belongs to a four-generation family with a total of three affected females and four affected males. The patient was initially diagnosed with retinitis pigmentosa (RP) at the age of 4 years. Genetic testing identified a heterozygous donor splice site mutation in intron 1 (IVS1 + 1G > A) of the retinitis pigmentosa GTPase regulator gene. The father of the proband was diagnosed with RP when he was a young child. The sister of the proband, evaluated at the age of 6 years, showed macular pigmentary changes.
  
  
  CONCLUSIONS
  Although carriers of XLRP are usually asymptomatic or have a mild disease of late onset, the proband presented here exhibited an early-onset, aggressive form of the disease. It is not clear why some carrier females manifest a severe phenotype. A better understanding of the genetic processes involved in the penetrance and expressivity of XLRP in heterozygous females could assist in providing the appropriate counseling to affected families.
authors.affiliation: a Department of Ophthalmology , University of Florida , Gainesville , FL , USA.
authors.forename: Amde Selassie
authors.initials: AS
authors.lastname: Shifera
authors.forename: Christine Nichols
authors.initials: CN
authors.lastname: Kay
mesh_terms: D002648:Child; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D008040:Genetic Linkage; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests; D014794:Visual Fields
chemical_list: D005136:Eye Proteins; D022821:RNA Splice Sites; C099929:RPGR protein, human
keywords: Manifesting carrier; X-linked retinitis pigmentosa; retinitis pigmentosa; retinitis pigmentosa GTPase regulator