Correlation of genetic and clinical findings in Spanish patients with X-linked juvenile retinoschisis.
OBJECTIVE
X-linked juvenile retinoschisis (XLRS) is one of the most common causes of juvenile macular degeneration in males, characterized by microcystic changes, splitting within the inner retinal layer (schisis), and the presence of vitreous veils. This study was conducted to describe and further correlate specific genetic variation in Spanish patients with XLRS with clinical characteristics and additional ophthalmic complications.


METHODS
The study was performed in 34 Spanish families with XLRS, comprising 51 affected males. Thorough clinical ophthalmic and electrophysiological examinations were performed. The coding regions of the RS1 gene were amplified by polymerase chain reaction and directly sequenced. Haplotype analyses were also performed.


RESULTS
Twenty different mutations were identified. Ten of the 20 were novel and 3 were de novo mutational events. The most common mutation (p.Gln154Arg; 6/20) presented a common haplotype. RS1 variants did not correlate with ophthalmic findings and were not associated with additional ophthalmic complications.


CONCLUSIONS
The prevalent p.Gln154Arg mutation is first reported in this work and presents a common origin in Spanish patients with XLRS. In addition, de novo mutations mainly occur in CG dinucleotides. Despite the large mutational spectrum and variable phenotypes, no genotype-phenotype correlations were found. Identifying the causative mutation is helpful in confirming diagnosis and counseling, but cannot provide a prognosis.
Riveiro-Alvarez
Rosa
R
Department of Genetics, Fundacion Jimenez Diaz, Madrid, Spain. rriveiro@fjd.es
Trujillo-Tiebas
Maria-Jose
MJ
Gimenez-Pardo
Ascension
A
Garcia-Hoyos
Maria
M
Lopez-Martinez
Miguel-Angel
MA
Aguirre-Lamban
Jana
J
Garcia-Sandoval
Blanca
B
Vazquez-Fernandez del Pozo
Silvia
S
Cantalapiedra
Diego
D
Avila-Fernandez
Almudena
A
Baiget
Montserrat
M
Ramos
Carmen
C
Ayuso
Carmen
C