What are the genetic changes related to Fraser syndrome ?
Mutations in the FRAS1, FREM2, or GRIP1 gene can cause Fraser syndrome. FRAS1 gene mutations are the most common cause, accounting for about half of cases of Fraser syndrome. FREM2 and GRIP1 gene mutations are each found in a small percentage of cases.  The FRAS1 and FREM2 proteins (produced from the FRAS1 and FREM2 genes, respectively) are part of a group of proteins called the FRAS/FREM complex. The GRIP1 protein (produced from the GRIP1 gene) ensures that FRAS1 and FREM2 get to the correct location of the cell to form the FRAS/FREM complex.  The FRAS/FREM complex is found in basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. This complex is particularly important during development before birth. One of the complex's roles is to anchor the top layer of skin by connecting its basement membrane to the layer of skin below. The FRAS/FREM complex is also involved in the proper development of other organs and tissues, including the kidneys, although the mechanism is unclear.  Mutations in any of these genes prevent formation of the FRAS/FREM complex. Lack of this complex in the basement membrane of the skin leads to detachment of the top layer of skin, causing blisters to form during development. These blisters likely impair the proper formation of certain structures before birth, leading to cryptophthalmos and cutaneous syndactyly. It is unknown how lack of the FRAS/FREM complex leads to kidney and genital abnormalities and other problems in Fraser syndrome.