Phenotype associated with mutation in the recently identified autosomal dominant retinitis pigmentosa KLHL7 gene.
OBJECTIVE
To characterize the clinical phenotype, with an emphasis on electrophysiologic findings, in a family with autosomal dominant retinitis pigmentosa caused by mutation in the recently identified KLHL7 gene.


METHODS
Eleven patients from a single family were selected from the Swedish retinitis pigmentosa register. Four patients had been examined 13 to 17 years earlier and underwent further ophthalmologic examination, including visual acuity, fundus inspection, Goldmann perimetry, full-field electroretinography (ERG), multifocal ERG, and optical coherence tomography. KLHL7 mutation was identified by sequence analysis.


RESULTS
In most examined family members, the fundus showed minor abnormalities. Full-field ERG demonstrated reduced cone and rod function, but rod responses were preserved in some patients late in life. Follow-up (<or=17 years) demonstrated slowly progressive retinal degeneration. In an adolescent family member, cone and rod function was initially normal, but retinitis pigmentosa was confirmed by electrophysiology 17 years later. Optical coherence tomography and multifocal ERG demonstrated macular abnormalities of varying degree among family members. Genetic analysis revealed a heterozygous exon 6 change (c.458C>T) in 7 family members.


CONCLUSIONS
Observed in 2 Scandinavian families to date, KLHL7 mutation has recently been associated with autosomal dominant retinitis pigmentosa. Clinical examination with long-term follow-up verified a phenotype with a varying degree of retinal photoreceptor dysfunction and, in some family members, with late onset and preserved rod function until late in life. Clinical Relevance Patients with minor retinal abnormalities and normal ERG findings early in life can harbor an autosomal dominant form of retinitis pigmentosa with a varying degree of visual impediment. Some patients with late onset may retain night vision for many years.
Hugosson
Therése
T
Department of Clinical Sciences, Ophthalmology, Lund University, Lund, Sweden. Therese.Hugosson@med.lu.se
Friedman
James S
JS
Ponjavic
Vesna
V
Abrahamson
Magnus
M
Swaroop
Anand
A
Andréasson
Sten
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000235:genetics*; D004596:Electroretinography; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012042:Registries; D012174:Retinitis Pigmentosa / Q000235:genetics*; D013548:Sweden; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D058609:Visual Field Tests; D014794:Visual Fields; D055815:Young Adult
D001324:Autoantigens; C505353:KLHL7 protein, human