NDP Human

Norrie disease is a rare X-linked recessive genetic disorder that primarily affects the eyes and almost always leads to blindness. It is caused by mutations in the Norrin cystine knot growth factor gene, also referred to as the Norrie Disease Pseudoglioma (NDP) gene . The disease manifests with vision impairment either at birth or within a few weeks of life, following an ocular event like retinal detachment, and is progressive through childhood and adolescence .

The NDP gene is responsible for encoding a protein called Norrin, which plays a crucial role in the development and maintenance of the retina and inner ear . Mutations in this gene disrupt the normal signaling pathways necessary for the formation of blood vessels in the retina, leading to the characteristic symptoms of Norrie disease .

The most prominent symptoms initially observed in Norrie disease are ocular. Initial characteristics are usually identified at birth or in early infancy, with parents often noticing abnormal eye features or that their child fails to show a response to light . The first visible finding is leukocoria, a grayish-yellow pupillary reflection that originates from a mass of disorganized tissue behind the lens . This material, which possibly includes an already detached retina, may be confused with a tumor and thus is termed pseudoglioma .

In addition to the congenital ocular symptoms, the majority of individuals afflicted by this disease develop progressive hearing loss caused by vascular abnormalities in the cochlea . Hearing loss usually begins in early childhood and may be mild at first before becoming more progressive by the third or fourth decade of life . Roughly 30-50 percent of those affected by the disease might encounter cognitive challenges, learning difficulties, incoordination of movements, or behavioral abnormalities .

Due to the X-linked recessive pattern of inheritance, Norrie disease affects almost entirely males . Only in very rare cases, females have been diagnosed with Norrie disease; cases of symptomatic female carriers have been reported . It is a very rare disorder that is not associated with any specific ethnic or racial groups, with cases reported worldwide . While more than 400 cases have been described, the prevalence and incidence of the disease still remain unknown .

Human recombinant Norrin is a synthetic form of the Norrin protein produced through recombinant DNA technology. This technology involves inserting the NDP gene into a host organism, such as bacteria or yeast, which then produces the Norrin protein . The recombinant Norrin can be used in research to better understand the molecular mechanisms underlying Norrie disease and to develop potential therapeutic interventions .

Research on Norrie disease focuses on understanding the molecular and cellular mechanisms disrupted by NDP gene mutations . Studies using human recombinant Norrin have provided insights into the signaling pathways involved in retinal and cochlear development . Potential therapeutic approaches include gene therapy to correct the underlying genetic defect and the use of recombinant Norrin to restore normal signaling pathways .