Homozygous deletion related to Alu repeats in RLBP1 causes retinitis punctata albescens.
OBJECTIVE
Retinitis punctata albescens (RPA) is an infrequently occurring form of autosomal recessive (and rarely dominant) retinal dystrophy featuring early-onset severe night blindness and tiny, dotlike, white deposits in the fundus. RPA is associated mostly with mutations in RLBP1 and occasionally in RHO, RDS, and RDH5. In this study, mutations were sought in RLBP1, which encodes the retinol binding protein CRALBP in patients with typical RPA.


METHODS
Clinical investigation included funduscopy, visual field testing, electroretinogram recording, and adaptometry. The 7 coding exons (3-9) of RLBP1 and the 15th (last) exon of ABDH2 were PCR amplified and sequenced. Long-distance PCR and cloning of genomic DNA were performed to characterize the deletion.


RESULTS
The study involved a 24-year-old Moroccan patient with typical RPA, born of first-cousin parents. He carried a 7.36-kb homozygous deletion encompassing the last 3 exons of RLBP1 (7, 8, and 9) and part of the intergenic region between RLBP1 and ABHD2, which lies downstream of RLBP1. This deletion abolishes the retinal binding site of CRALBP. The telomeric breakpoint of the deletion (in RLBP1 intron 6) is embedded in an Alu element, whereas the centromeric breakpoint (in the intergenic region) lies between two Alu elements placed in the opposite orientation.


CONCLUSIONS
Because of the high density of Alu elements in RLBP1, a systematic search should be made for deletions in this gene when one or both alleles lack point mutations, in the case of RPA or flecked retinal dystrophy.
Humbert
Ghyslaine
G
INSERM Unité 583, Institut des Neurosciences de Montpellier, Hôpital Saint-Eloi, BP 74103, 80 rue Augustin Fliche, 34091 Montpellier Cedex 5, France.
Delettre
Cécile
C
Sénéchal
Audrey
A
Bazalgette
Cécile
C
Barakat
Abdelhamid
A
Bazalgette
Christian
C
Arnaud
Bernard
B
Lenaers
Guy
G
Hamel
Christian P
CP
D000328:Adult; D020087:Alu Elements / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003241:Consanguinity; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009755:Night Blindness / Q000235:genetics*; D012162:Retinal Degeneration / Q000235:genetics*; D012173:Retinitis / Q000235:genetics*; D014794:Visual Fields
C020932:11-cis-retinal-binding protein; D002352:Carrier Proteins