New RPGR gene mutation produces an extended X linked RP syndrome

Researchers have warned against equating animal and human models of X linked retinitis pigmentosa (XLRP) after finding a new mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene associated with a unique, extended XLRP syndrome in one family. The syndrome encompasses recurrent middle ear and upper respiratory tract infections (URTIs), hearing loss, and impaired sight. Compromised ciliary function may be the cause.

The researchers found a G576C substitution in the RPGR gene, causing a glycine to arginine shift in the GTPase regulator in the proband—a 10 year old white boy with hearing loss referred for confirmation of suspected RP or Usher syndrome, present in a relative four generations previously. The mutation occurred in his younger brother, who had recurrent URTIs and ear infections and was developing hearing loss and sight problems; their maternal grandmother, who had late RP and 15 years’ hearing loss after decades of recurrent middle ear infections; and their mother, who had no symptoms. It was absent in the boys’ father and sister, who were symptom free, and in over 200 normal human chromosomes.

Native GTPase regulator was expressed in human retinal, bronchial, and sinus epithelium and in human and monkey cochlea epithelium, consistent with the range of phenotypic symptoms in subjects with the mutation.

The findings were based on full ophthalmological examinations; hearing tests; clinical data on infections from patient records; and molecular genetic analysis in the six key family members.

Hearing loss and recurrent middle ear and upper respiratory tract infections are rare in XLRP.