Hypomyelination and congenital cataract (Hypomyelination and congenital cataract) - Gen FAM126A  

The hypomyelination and congenital cataract is a hereditary disease that affects the nervous system and eyes. This disease belongs to a group of genetic disorders called leukoencephalopathies. The leukoencephalopathies involve abnormalities in the white matter of the brain. White matter consists of nerve fibers covered by myelin, which insulates nerve fibers and promotes rapid transmission of nerve impulses. This disease is caused by a decreased ability to form myelin. In addition, people affected are often born with cataracts in both eyes.

Generally, affected individuals have normal development during the first year of life. Thereafter, these individuals show a slow development. Eventually they have atrophy in the legs and many people will eventually require a wheelchair. Weakness in the muscles of the trunk and progressive scoliosis hurts even walking in some individuals. Most people with congenital cataracts manifest hypomyelination and peripheral neuropathy. In addition, those affected often have dysarthria and mild to moderate intellectual disability.

This process is due to mutations in the FAM126A gene, located on the short arm of chromosome 7 (7p15.3). This gene encodes hicina protein, which is expressed throughout the nervous system. It is believed that hicina is involved in the formation of myelin that protects nerves and promotes the efficient transmission of nerve impulses. The hicina also is active in the lens of the eye, heart and kidneys. However, the function of the protein in these tissues is not clear.

They have been described at least four mutations in the gene responsible for hypomyelination FAM126A and congenital cataract. Most mutations eliminate a large part of the gene or create an early signal stop coding hicina. These mutations encoding inhibit any functional protein. A particular mutation FAM126A gene encoding allows reduced amounts of this protein. This mutation replaces the amino acid leucine by the amino acid proline at position 53 in the protein hicina (Leu53Pro or L53P). Leu53Pro people with the mutation usually show milder than those with mutations that inhibit protein coding hicina any symptoms. An interruption in coding hicina alter its role in the formation of myelin, leading to neurological problems such as difficulty walking and intellectual disabilities. However, it is unclear how hicina deficiency results in the presence of cataracts in both eyes since birth in affected individuals. Neurological problems and cataracts are the characteristic features observed in people with hypomyelination and congenital cataract.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with congenital cataract and hypomyelination, by complete PCR amplification of the exons of the FAM126A 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).