Background: To report the co-existence of novel biallelic PDE6A mutations
and heterozygous RPGR mutation in a Chinese female patient with retinitis pigmentosa
(RP), and to analyze the intrafamilial phenotypic diversity.
Methods: Three patients with retinopathy and four healthy family members were
included in genetic and clinical analyses. Personal medical records were obtained from
another four unaffected female family members who refused blood donation. Family
history was carefully recorded. Each patient received comprehensive ophthalmic tests.
Targeted next-generation sequencing (NGS) approach was performed on the proband to
determine the retinopathy causative mutation for this family. In silico analysis was also
applied to analyze the pathogenesis of identified mutations.
Results: The two recruited male patients were diagnosed with RP, and the female
patient RP sine pigmento (RPSP). Genetic assessments revealed a recurrent RPGR
mutation, c.1926_1927insA, carried by all three patients and segregated the disease
status. Three other unaffected female family members were confirmed as carriers for the
identified RPGR mutation, and another four as obligate carriers. Interestingly, of all the
eight female RPGR mutation carriers in this family, only one female developed retinal
dystrophy. Comprehensive genetic analysis of this patient unraveled additional biallelic
PDE6A mutations, c.[1066-9delT];[2324delG], carried solely by this individual.
Conclusions: Taken together, we hypothesize that the phenotypic variability presented
by female RPGR mutation carriers may be attributed to the co-existence of other
disease-causative mutations. Our study also emphasizes the importance of
comprehensive genetic analysis in these female carriers, which will contribute to better
diagnosis, prognosis, and treatment for these patients.