Fraser syndrome ... (Fraser syndrome) - Genes FRAS1, FREM2, or GRIP1.
Fraser syndrome is a rare disorder characterized by Cryptophthalmos, cutaneous syndactyly and genitourinary abnormalities. Other tissues and organs may also be affected. Depending on the severity of signs and symptoms, affected individuals may die before or shortly after birth or live through childhood or adulthood.
The Cryptophthalmos is the most common abnormality in people with Fraser syndrome. In general, both eyes are completely covered by skin, but in some cases, only one eye is covered or one or both eyes are partially covered. Another feature that includes Cryptophthalmos is the malformation of the eyes. For example, the eyeballs may adhere to the overlying skin, or may occur microphthalmia or anophthalmia. These abnormalities can cause loss of vision. Affected individuals may have other problems related to eye development, including the absence of eyebrows or eyelashes. Meanwhile, cutaneous syndactyly occurs normally in both hands and feet. In most people with this feature, the skin between the fingers and toes fuses. Genitourinary abnormalities may include cryptorchidism in males or ambiguous genitalia. The most common abnormality in the urinary tract Fraser syndrome is renal agenesis. Besides kidney agenesis, those affected may have other problems or abnormalities in kidney bladder and other parts of the urinary tract.
Other signs and symptoms may be involved in Fraser syndrome, including heart or other anomalies of the larynx or other parts of the respiratory tract. Some affected individuals have facial abnormalities which may include ear or nose or cleft lip with or without cleft palate.
This disease is due to mutations in FRAS1, FREM2 or GRIP1 genes.
The proteins encoded by the genes FRAS1, located on the long arm of chromosome 4 (4q21.21) and FREM2, located on the long arm of chromosome 13 (13q13.3) are part of a group of proteins called the FRAS / FREM complex . The FRAS / FREM complex is in basement membranes. This resort is particularly important during development before birth. One function of the complex is to bind the top layer of the skin by connection of the basement membrane to the lower layer. The FRAS / FREM complex is also involved in the proper development of other organs and tissues, including the kidneys, although the mechanism is unclear.
They have identified at least 24 mutations in the gene FRAS1 and at least 2 mutations in the gene FREM2 in people with Fraser syndrome. Mutations in the gene FRAS1 approximately half of cases of this disease. Most mutations in the gene result FRAS1 encoding an abnormal protein with little or no function. It is likely that this protein is rapidly destroyed, preventing complex formation FRAS / FREM. Mutations in any of these genes prevent the formation of complex FRAS / FREM. The absence of this complex in the basement membrane of the skin causes the detachment of the top layer of the skin, causing blisters during development. These blisters will likely alter the formation of certain structures before birth, leading to Cryptophthalmos and cutaneous syndactyly. It is unclear how the absence of FRAS / FREM complex leads to kidney abnormalities, genital and other problems in Fraser syndrome.
The GRIP1 gene, located on the long arm of chromosome 12 (12q14.3), encodes a protein which is capable of binding other proteins and is important for the correct location of proteins in cells. For example, GRIP1 protein directs the proteins encoded by the genes FREM2 FRAS1 and to the correct region of the cell so that they constitute the FRAS / FREM complex. In addition, the protein directs GRIP1 necessary for the synapses between neurons where communication cell to cell proteins occurs. This protein may also be involved in the development of neurons. They have identified at least 2 mutations in the gene GRIP1 people with Fraser syndrome. These mutations alter the genetic map GRIP1 encoding the protein. As a result, it is likely that if GRIP1 protein is encoded, it is not functional.
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 performed in IVAMI: in IVAMI perform detection of mutations associated with Fraser syndrome, by complete PCR amplification of the exons of FRAS1, FREM2 and GRIP1, respectively, and subsequent sequencing genes.
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).