Haider et al. (2000) carried out a study on 102 premature newborns of Kuwaiti Arab origin to research the presence of Norrie disease (ND) gene and replicate the findings in a diverse population/racial group. Controls constituted 55% (56) of the newborns and they demonstrated normal eyes. Retinopathy of prematurity (ROP) regressed spontaneously throughout stage 1-3 in 34% of cases (35), whereas 11 cases (11%) experienced ROP that progressed to advanced stages. The screened premature newborns presented the R121W mutation of exon 3 in the ND gene; however, 98% of these newborns possessed the genotype (PP) of the second mutation [L108P]. Furthermore, the (LL) genotype was found in only one of the 56 normal infants. Haider et al. (2000) concluded that the Kuwaiti population is genetically homogenous due to the detection of genotype (PP) at codon 108 in nearly all controls and ROP cases. Moreover, no correlation was found among the risk of severe ROP and the presence or absence of missense mutations of the ND gene. Later, Haider et al. (2001) screened 210 Kuwaiti premature newborns for two Norrie disease (ND) gene mutations (A105T and Va160Glu) using PCR-RFLP and allele-specific PCR techniques. In the 210 cohort, 115 babies had no eye problems and were employed as controls, while 95 babies were found to have Retinopathy of Prematurity (ROP). It was found that from the 95 ROP cases, the disease in 71 cases regressed spontaneously at or before stage 3, whereas in the remaining 24 cases the disease progressed to stages 4 and 5. The AA genotype of the missense mutation (A105T) was found in 96% of controls and 87% of ROP cases with no significant distinction among ROP cases that regressed spontaneously and those that progressed to higher stages. As for the second mutation (Va160Glu), no association was found among the genotype and the ROP cases that progressed to higher stages. Furthermore, Haider et al. (2002) studied the effect of mutations in the Norrie disease gene on the progression of Retinopathy of Prematurity (ROP) disease to advanced stages. The study included screening for a novel C597A polymorphism and an additional mutation of the ND gene (C110G). The cohort included 210 Kuwaiti premature newborns babies (103 males and 107 females) from the Maternity Hospital in Kuwait with a mean birth weight of 1,267g and a mean gestational age of 30.7 weeks. Of the 210 Kuwaiti babies, 115 had no eye problems and were employed as controls, while 95 babies were found to have ROP. Out of the 95 cases, 71 cases (75%) experienced spontaneous regression at/before stage 3 of the disease, whereas 24 cases (25%) experienced disease progression to advanced stages 4 or 5. The incidence rate of the AA genotype of the C597A polymorphism was found to be the least in ROP cases with spontaneous regression (0%), while it was found to be the highest in ROP cases with an advanced-stage (83.3%) and it reached 10.4% in normal controls. Hiader et al (2002) found no significant association of the C110G mutation with the onset of ROP or progression to advanced stages.

Alnaggar et al. (2006) described the molecular defects in the Norrie disease (ND) gene in a Kuwaiti Bedouin family with three sibs affected with Norrie disease. Affected members had the R121W mutation, caused by a C>T substitution in exon 3 of the NDP gene.

Khan et al. (2004) diagnosed two brothers with severe Norrie disease. DNA sequencing demonstrated a novel missense mutation (703G>T) that significantly alters predicted protein structure. Later, Khan et al. (2008) studied the correlation of ophthalmic examination with carrier status in females for the severe C95F. The studied group included six potential carriers and one obligate carrier from a family harboring the mutation. A full ophthalmic examination was independently performed for the seven asymptomatic family members. Three carriers were identified by molecular genetics, and all had peripheral retinal abnormality. However, three of the four genetically identified non-carriers also exhibited peripheral retinal abnormality. Two of these non-carriers with retinal findings were the offspring of confirmed non-carriers. The genetically identified non-carrier with a normal peripheral retinal examination was the daughter of an obligate carrier. Accordingly, the presence of peripheral retinal changes was not considered informative of the carrier status of the family members hinting for additional loci that could be implicated in the phenotypic expression.