Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity

Retinopathy of prematurity (ROP) is a leading cause of blindness in prematu re children. It is a multifactorial disorder which causes fibrovascular tis sue changes that affect the retina in low birth-weight and short gestationa l age infants. To determine the prevalence of Norrie disease (ND) gene muta tions, clinical examination and molecular genetic analyses were performed i n 100 pre-term babies of different ethnic backgrounds who developed advance d ROP. The leukocyte DNA was extracted, amplified by the polymerase chain r eaction (PCR), and analyzed by single-strand conformation polymorphism (SSC P), G/T and C/A scanning, and by DNA sequencing. All three exons, including splice sites and the 3'-untranslated region, were screened. Of the 100 pat ients analyzed, 2 patients with advanced ROP showed a mobility shift in the DNA. In 1 patient, this mobility shift was caused by the insertion of an a dditional 12-bp CT repeat in exon 1, and in the second patient, there was a 14-bp deletion in the same exon of the ND gene, as evidenced by direct seq uencing of the amplified products. Similar analyses of exons 2 and 3 and th e 3'-untranslated region failed to detect additional mutations in the gene. None of the 130 normal. unrelated controls revealed similar changes. Takin g into account the above results, as well as those of other studies. it app ears that the ND gene mutations can account for 3% of cases of advanced ROP . Although the ND gene is not frequently involved in advanced ROP, the pres ent large-scale study further supports the hypothesis that genetic influenc es may play an important role in the development of severe ROP in some prem ature infants.