Long-term follow-up of a family with dominant X-linked retinitis pigmentosa.
OBJECTIVE
To document the progression of disease in male and female members of a previously described family with X-linked dominant retinitis pigmentosa (RP) caused by a de novo insertion after nucleotide 173 in exon ORF15 of RPGR.


METHODS
The clinical records of 19 members of family UTAD054 were reviewed. Their evaluations consisted of confirmation of family history, standardised electroretinograms (ERGs), Goldmann visual fields, and periodic ophthalmological examinations over a 23-year period.


RESULTS
Male members of family UTAD054 had non-recordable to barely recordable ERGs from early childhood. The males showed contracted central fields and developed more severe retinopathy than the females. The female members showed a disease onset delayed to teenage years, recordable but diminishing photopic and scotopic ERG amplitudes in a cone-rod pattern, progressive loss and often asymmetric visual fields, and diffuse atrophic retinopathy with fewer pigment deposits compared with males.


CONCLUSIONS
This insertion mutation in the RPGR exon ORF15 is associated with a RP phenotype that severely affects males early and females by 30 years of age, and is highly penetrant in female members. Families with dominant-acting RPGR mutations may be mistaken to have an autosomal mode of inheritance resulting in an incorrect prediction of recurrence risk and prognosis. Broader recognition of X-linked RP forms with dominant inheritance is necessary to facilitate appropriate counselling of these patients.
Wu
D M
DM
Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48105, USA.
Khanna
H
H
Atmaca-Sonmez
P
P
Sieving
P A
PA
Branham
K
K
Othman
M
M
Swaroop
A
A
Daiger
S P
SP
Heckenlively
J R
JR
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003623:Dark Adaptation / Q000502:physiology; D018450:Disease Progression; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics*; D012030:Refractive Errors; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D012684:Sensory Thresholds; D014792:Visual Acuity; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
D005136:Eye Proteins; C099929:RPGR protein, human