Meckel syndrome (Meckel syndrome) - Genes B9D1, B9D2, CC2D2A, CEP290, MKS1, RPGRIP1L, TMEM216, TMEM67.
Meckel syndrome is a disorder with serious signs and symptoms that affect many parts of the body. The most common features include enlarged kidneys with numerous fluid - filled cysts, encephalocele occipital, polydactyly and hepatic fibrosis. Other signs and symptoms of the syndrome vary widely between individuals affected and include central nervous system abnormalities such as defects in the neural canal. These defects occur when the neural canal does not close completely during the first weeks of embryonic development. Meckel syndrome can also cause problems with the development of the eyes and other facial features, heart, bones, urinary system and genitals. Due to serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Very often affected children die from respiratory problems or kidney failure.
Meckel syndrome can be caused in about 75% of the cases by mutations in:
- The B9D1 gene, located on the short arm of chromosome 17 (17p11.2).
- The B9D2 gene, located on the long arm of chromosome 19 (19q13.2).
- The CC2D2A gene, located on the short arm of chromosome 4 (4p15.32).
- The CEP290 gene, located on the long arm of chromosome 12 (12q21.32).
- The MKS1 gene, located on the long arm of chromosome 17 (17q22).
- The RPGRIP1L gene, located on the long arm of chromosome 16 (16q12.2).
- The TMEM216 gene, located on the long arm of chromosome 11 (11q13.1).
- The TMEM67 gene, located on the long arm of chromosome 8 (8q22.1).
In other cases, the genetic cause is unknown. Mutations in other genes have been identified in people with similar characteristics of Meckel syndrome, although it is not clear whether these people really have Meckel syndrome or a related condition known as "Meckel - like phenotype."
Proteins produced from these genes play a role in the structure and ciliary function. The cilia are important for structure and function of many cell types, including brain cells and certain cells in the kidneys and liver.
Mutations in genes associated with Meckel syndrome lead to problems with the structure and function of the cilia. Defects in these cellular structures will likely disrupt important chemical signaling pathways during early development. Although it is believed that faulty cilia are responsible for most of the characteristics of this disease, it is unclear how lead to specific developmental abnormalities of the brain, kidneys and other body parts.
This disease is inherited in an autosomal recessive pattern, that is, 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 the detection of mutations associated with Meckel syndrome, by complete PCR amplification of the exons of B9D1, B9D2, CC2D2A, CEP290, MKS1, RPGRIP1L, TMEM216 and TMEM67 genes, respectively, 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).