Norrie disease ... (Norrie disease) - Gen NDP.  

Norrie's disease is an inherited eye disorder that leads to blindness in male infants at birth or shortly after birth. The involvement occurs as a result of abnormal development of the retina, with masses of immature cells that accumulate in the back of the eye. As a result, pupils are white when light shines on them, a sign called leucocoria. The iris, or the entire eyeball, can shrink and deteriorate during the first months of life, being able to develop cataracts.

Approximately one third of people with the disease develop progressive hearing loss and developmental delays in skills. Other features may include mild to moderate mental retardation, often with psychosis and disorders that may affect the circulation, respiration, digestion, excretion, or reproduction.

This process is due to mutations in the gene NDP (Xp11.4). This gene encodes the protein Norrin. This protein is involved in the Wnt cascade, a sequence of steps that affect the way in which cells and tissues develop. In particular, it appears that the protein plays a critical role in the specialization of retinal cells for their unique sensory abilities. It is also involved in establishing a blood supply to the tissues of the retina and inner ear, and the development of other body systems. In order to initiate the cascade of Wnt protein is connected to another protein called frizzled-4. The protein Norrin and frizzled-4 receptor involved in development processes that are thought to be crucial for normal eye development and other body systems. In particular, it seems that Norrin plays a critical role in the specialization of cells in the retina and the establishment of a blood supply to the retina and inner ear.

They have identified more than 75 mutations in the NDP gene in people with Norrie disease. These mutations affect the ability of the Norrin protein to bind to frizzled-4, interfering with the specialization of retinal cells for their unique sensory function. As a result, the masses of immature retinal cells accumulate in the back of the eye. The impaired function of Norrin in establishing the blood vessels that supply the eye causes that eventually some of the tissues deteriorate. Specific anomalies and their severity depend on the type and location of the mutation gene NDP. Mutations which remove portions of the gene NDP prevent the production of Norrin causing serious problems affecting many body systems, in addition to the eyes. Mutations which eliminate or change the individual amino acids typically result in less overall impact.

Norrie's disease is inherited as a recessive X - linked pattern A condition is considered X - linked if the mutated gene that causes the disorder is located on the X chromosome in males, an altered copy of the gene in each cell is sufficient to cause disease. In women, a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X - linked recessive disorders much more frequently than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome.

In X - linked recessive inheritance, a woman with an altered copy of the gene in each can transmit the gene, but generally have no signs and symptoms of the disease. However, in rare cases among women who have shown some retinal abnormalities or mild hearing loss associated with Norrie disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Norrie disease by the complete PCR amplification of exons NDP gene and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).