Retinal phenotype-genotype correlation of pediatric patients expressing mutations in the Norrie disease gene.
OBJECTIVE
To correlate the ophthalmic findings of patients with pediatric vitreoretinopathies with mutations occurring in the Norrie disease gene (NDP).


METHODS
One hundred nine subjects with diverse pediatric vitreoretinopathies and 54 control subjects were enrolled in the study. Diagnoses were based on retinal findings at each patient's first examination. Samples of DNA from each patient underwent polymerase chain reaction amplification and direct sequencing of the NDP gene.


RESULTS
Eleven male patients expressing mutations in the NDP gene were identified in the test group, whereas the controls demonstrated wild-type NDP. All patients diagnosed as having Norrie disease had mutations in the NDP gene. Four of the patients with Norrie disease had mutations involving a cysteine residue in the cysteine-knot motif. Four patients diagnosed as having familial exudative vitreoretinopathy were found to have noncysteine mutations. One patient with retinopathy of prematurity had a 14-base deletion in the 5' untranslated region (exon 1), and 1 patient with bilateral persistent fetal vasculature syndrome expressed a noncysteine mutation in the second exon.


CONCLUSIONS
Mutations disrupting the cysteine-knot motif corresponded to severe retinal dysgenesis, whereas patients with noncysteine mutations had varying degrees of avascular peripheral retina, extraretinal vasculature, and subretinal exudate.


CONCLUSIONS
Patients exhibiting severe retinal dysgenesis should be suspected of carrying a mutation that disrupts the cysteine-knot motif in the NDP gene.
Wu
Wei-Chi
WC
Associated Retinal Consultants, William Beaumont Hospital, 3535 W. 13 Mile Road, Royal Oak, MI 48073, USA.
Drenser
Kimberly
K
Trese
Michael
M
Capone
Antonio
A
Dailey
Wendy
W
D000595:Amino Acid Sequence; D001766:Blindness / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D003638:Deafness / Q000175:diagnosis / Q000235:genetics*; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012160:Retina / Q000002:abnormalities* / Q000473:pathology; D018630:Vitreoretinopathy, Proliferative / Q000175:diagnosis / Q000235:genetics
D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins; D003545:Cysteine