Frequency of RP2 and RPGR Mutations in Male Sibships and in Sporadic Male Patients Affected With Retinitis Pigmentosa

Abstract

Purpose:: To evaluate the frequency of RPLX genes in male sporadic cases and male sibships without transmission of the disease in the maternal branch.

Methods:: Seven families with male affected brothers but without any relative affected with RP and 26 sporadic male cases were ascertained. Isolated male cases were suspected of having XLRP on the basis of clinical risk factors e.g. severe RP with onset in the first decade, rapid progression and visual acuity 2/10. The mother and/or closely related females of the affected male accepted to undergo an ophthalmoscopic examination in 13/26 families. In ten out of the thirteen families clinical symptoms suggestive of the XLRP carrier state were evidenced in at least one female. The RP2 and RPGR (including ORF15) genes were screened for mutations by direct sequencing.

Results:: RP2 or RPGR mutations were found in 2/7 male sibships (28.6%), 9/26 sporadic male cases (34.6%). Only one RP2 mutation was identified (n= 1 sporadic case). The ten other mutations were found in the RPGR gene in either the ORF15 exon (n=8) or in the 19 other exons (n=2).

Conclusions:: We show here that more than one third of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30. Besides, the poor implication of RP2 compared to RPGR in male sporadic cases reflects the selection bias of our panel. Indeed, male sporadic were selected not only on the severity of the phenotype but also on the existence of refractive errors in sisters or mothers such as severe or asymmetric myopia. These findings are by far more common in RPGR carriers.

Keywords: candidate gene analysis • retinal degenerations: hereditary • genetics