Ruifang Sui

Phenotypic expression of X-linked retinoschisis in Chinese families with mutations in the RS1 gene

To assess the clinical features of and identify genetic defects in six Chinese families with X-linked retinoschisis (XLRS). Patients were recruited from ophthalmic clinics in Peking Union Medical College Hospital. A cohort of six unrelated families was identified. Clinical evaluation was performed on eight affected males (six probands) and five female carriers. Genomic DNA was extracted from peripheral leukocytes. All exons and the flanking introns of the RS1 gene were amplified by polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control X chromosomes were screened by direct sequencing to exclude nonpathogenic polymorphisms. Typical foveal schisis was found in all eight patients, while peripheral schisis was noted in six patients. The six probands displayed electronegative electroretinography (ERG) in the standard combined response, while the remaining two patients showed non-recordable waveforms. Two novel mutations (W112X and S134P) and three previously identified missense mutations (R102Q, R200H, and R213W) were found. None of these novel nucleotide variations were observed in any of 100 ethnically matched control chromosomes. Chinese patients with XLRS displayed variability in phenotypes. Novel mutations in RS1 were associated with these patients. Identification of the disease-causing mutations in suspected families can help to confirm the diagnosis for the patients and recommend genetic counseling for the female carriers. In addition, genetic testing could provide important information for future treatment.

RDH5 retinopathy (fundus albipunctatus) with preserved rod function.

Purpose: The aim of this study is to characterize the clinical features of four unrelated Chinese patients with retinal dehydrogenase 5 (RDH5) retinopathy (fundus albipunctatus) and to identify the genetic defects underlying this disorder. Methods: Complete ophthalmic examinations, including slit-lamp biomicroscopy, dilated indirect ophthalmoscopy, spectral domain optical coherence tomography, and full-field electroretinography were performed. Genomic DNA was prepared from peripheral venous leukocytes. Polymerase chain reaction and direct sequencing were used to screen the coding exons and exon/intron boundaries of the RDH5 gene (11-cis-retinol dehydrogenase). Results: Four patients with RDH5 retinopathy, including two 6-year-old boys, from 4 unrelated Chinese families were recruited in this study. A novel c.832C>T (p.Arg278Ter) nonsense mutation of the RDH5 gene was identified in one 6-year-old boy, who has a compound heterozygous mutation with c.928delC/InsGAAG (p.Leu310GluVal). Homozygous Leu310GluVal mutations were identified in 2 male patients including the other 6-year-old boy. The other patient was a 29-year-old woman in whom compound heterozygous changes c.500G>A (p.Arg167His) and Leu310GluVal in RDH5 were identified. All patients manifested the fundus phenotype of fundus albipunctatus. Electroretinograms recorded in 1 boy (Case 3) showed scotopic waveforms within normal range under standard conditions and no change after prolonged dark adaptation. Scotopic waveforms were within the normal range for Case 4 while higher amplitudes (30% increase) were recorded after prolonged dark adaptation. The two adult patients had depressed scotopic electroretinogram responses under standard conditions. Optical coherence tomography showed discrete highly reflective lesions extending from the retinal pigment epithelium to the level of the external limiting membrane. Conclusion: A novel c.832C>T (p.Arg278Ter) nonsense mutation in RDH5 was identified. A specific mutation, Leu310GluVal, was seen in the homozygous state in one adult male and one boy and in the heterozygous state in one female adult and one boy with RDH5 retinopathy, suggesting a common mutation. Preserved rod function was observed in one young subject in this study.

Axenfeld-Rieger syndrome in monozygotic twins.

Two teenaged monozygotic twin sisters with Axenfeld-Rieger syndrome (ARS) were referred to our center for uncontrolled glaucoma from the local hospital in December 2006. At presentation, typical components of ARS could be found in both patients, including iris anomaly, maxillary hypoplasia, hypodontia, and umbilical skin fold. Both sisters received trabeculectomy in both the eyes later in our center. Intraocular pressure was well controlled in both the eyes in both patients 1 year after the surgeries. No mutations were found by direct sequencing of PITX2 and FOXC1 genes, in the twin sisters. As far as we know, no earlier report has described monozygotic twins with ARS in the international literature.