X-linked dominant RPGR gene mutation in a familial Coats angiomatosis

Abstract

Background: Retinitis Pigmentosa (RP) is the most frequent retinal hereditary disease and every kind of transmission pattern has been described. The genetic etiology of RP is extremely heterogeneous and in the last few years the large application of Next Generation Sequencing (NGS) approaches improved the diagnostic yield, elucidating previously unexplained RP causes and new genotype-phenotype correlations. The objective of this study was to reevaluate a previously reported family affected by Coats'-type RP without genetic diagnosis and to describe the new genetic findings.

Case presentation: Cohort, prospective, and single-center observational family case. Three individuals of a family, consisting of a mother and four sons, with a Coats phenotype were revaluated after 25 years of clinical follow-up using visual acuity tests, ophthalmoscopy, Goldmann visual field, electroretinography (ERG), and spectral domain-optical coherence tomography (SD-OCT). Specifically, a RP NGS panel was performed on one member of the family and segregation analysis was required for the other affected and unaffected members. NGS analysis disclosed a RPGR (Retinitis Pigmentosa GTPase Regulator) gene truncating variant segregating with the phenotype in all the three affected members. RPGR mutations are reported as causative of an X-linked RP.

Conclusions: This is the first reported family with a Coats'-type RP associated to a RPGR mutation and segregating as a dominant X-linked disease, confirming the hypothesis of the genetic origin of this condition and expanding the phenotypic spectrum of diseases caused by RPGR gene mutations. The Authors suggest RPGR gene screening mutations in patients presenting this phenotype.

Keywords: Case report; Coats vasculopathy; Coats’-type retinitis pigmentosa; Hereditary disease; RPGR- XLRP- Coats’-like retinitis.

Fig. 1

Pedigree of the family. a Black circle and squares indicate affected individuals. Black arrow indicates the proband who underwent NGS panel (III:1). Black lines at the top indicates available DNAs for segregation analysis (III:2, III:3 and II:2). b Sanger Sequencing Electropherograms showing on the top the proband (III:1) genotype of RPGR variant (black arrow) and below the wild-type (WT) genotype

Fig. 2

Images of the patient II:1 (mother). a/b The retinography and infrared photo show retinal exudations found from the center to the peripheral zones up to 2 papillary diameters and peripheral exudative retinal detachment (ERD) in the inferior and temporal sectors of right eye. c/d The retinal ultrasound and fluorescein angiography (FA) highlight exudative retinal detachment (ERD) area adjacent to retinal angiomatosis (RA) in the inferior and temporal sectors; hypo/anechogenic and hyperfluorescent areas, respectively. e The spectral domain-optical coherence tomography (SD-OCT) examination shows deposits of star-like hyper-reflective exudates (DSL) mainly present in the macular region. The photoreceptor layer (PL) is visible only in a portion of the macula in the patient affected from retinitis pigmentosa (RP)

Fig. 3

Spectral domain-optical coherence tomography (SD-OCT) of the III:1 patient (brother). Cystoid macular oedema (CMO) with areas of exudative vasculopathy (EV) for spongy appearance of the macular region in right eye. The photoreceptor layer (PL) is visible only in fovea of the patient affected from retinitis pigmentosa (RP)