Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis.
OBJECTIVE
X-linked juvenile retinoschisis (XLRS) is a vitreoretinal dystrophy characterized by schisis (splitting) of the inner layers of the neuroretina. Mutations within the retinoschisis (RS1) gene are responsible for this disease. The mutation spectrum consists of amino acid substitutions, splice site variations, small indels, and larger genomic deletions. Clinically, genomic deletions are rarely reported. Here, we characterize two novel full exonic deletions: one encompassing exon 1 and the other spanning exons 4-5 of the RS1 gene. We also report the clinical findings in these patients with XLRS with two different exonic deletions.


METHODS
Unrelated XLRS men and boys and their mothers (if available) were enrolled for molecular genetics evaluation. The patients also underwent ophthalmologic examination and in some cases electroretinogram (ERG) recording. All the exons and the flanking intronic regions of the RS1 gene were analyzed with direct sequencing. Two patients with exonic deletions were further evaluated with array comparative genomic hybridization to define the scope of the genomic aberrations. After the deleted genomic region was identified, primer walking followed by direct sequencing was used to determine the exact breakpoints.


RESULTS
Two novel exonic deletions of the RS1 gene were identified: one including exon 1 and the other spanning exons 4 and 5. The exon 1 deletion extends from the 5' region of the RS1 gene (including the promoter) through intron 1 (c.(-35)-1723_c.51+2664del4472). The exon 4-5 deletion spans introns 3 to intron 5 (c.185-1020_c.522+1844del5764).


CONCLUSIONS
Here we report two novel exonic deletions within the RS1 gene locus. We have also described the clinical presentations and hypothesized the genomic mechanisms underlying these schisis phenotypes.
Ophthalmic Genetics and Visual Function Branch, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD.
Leera
L
D'Souza
Catherine
C
Cukras
Christian
C
Antolik
Candice
C
Craig
Ji-Yun
JY
Lee
Hong
H
He
Shibo
S
Li
Nizar
N
Smaoui
James F
JF
Hejtmancik
Paul A
PA
Sieving
Xinjing
X
Wang
D002648:Child; D019457:Chromosome Breakage; D005091:Exons / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005654:Fundus Oculi; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D041441:Retinoschisis / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D041623:Tomography, Optical Coherence
D005136:Eye Proteins; C108726:RS1 protein, human