X-linked retinoschisis: novel mutation in the initiation codon of the XLRS1 gene in a large family.
OBJECTIVE
To describe a novel point mutation in the initiation codon of the XLRS1 gene in a large family and the clinical features of males affected with X-linked juvenile retino-schisis.


METHODS
Genealogic investigation and mutation screening of the XLRS1 gene were performed for a 4-generation family consisting of 72 members. Affected males were evaluated clinically between 1986 and 2004 with up to 18 years of follow-up.


RESULTS
We identified a novel point mutation (1A>T transversion) in the initiation codon of the XLRS1 gene in affected males resulting in an amino acid substitution of methionine to leucine (Met1Leu), therefore abolishing the translation initiation Met codon.


CONCLUSIONS
Identification of the disease-causing mutation in this family with long-term follow-up allows for earlier and more accurate identification of individuals at risk for this inherited progressive macular degeneration, provides for more accurate genetic counseling, and contributes to our understanding of the pathophysiology of this disorder.
Kim
David Y
DY
Henry and Corinne Bower Laboratory, Wills Eye Hospital and the Eye Research Institute, 211 South 9th Street, Room 402, Philadelphia, PA 19107, USA.
Neely
Kimberly A
KA
Sassani
Joseph W
JW
Vrabec
Tamara R
TR
Tantri
Avinash
A
Frost
Arcilee
A
Donoso
Larry A
LA
D018387:Codon, Initiator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D041441:Retinoschisis / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity
D018387:Codon, Initiator; D005136:Eye Proteins; C108726:RS1 protein, human