CCL cataracts are embryonic in origin, developing during the time when gamma-crystallin genes are active. The gamma E-crystallin gene is a pseudogene and the mutation in its promoter reactivates its activity 10-fold. It is postulated that overexpression of the gamma-crystallin fragment is responsible for the nuclear opacification.
Mutations in at least 3 genes have been associated with this type of cataract. In some families the mutations are in the CRYGC gene (2q33-q35), and in others mutations in CRYBB2 (22q11.2-q12.2) seem to be responsible. It is of interest that one form of congenital cerulean cataract, CCA3 (608983), found in a single family, results in mutations in CRYGD also located at 22q11.2-q12.2. A five-generation Chinese family has been reported in which mutations in GJA3 (13q12.11) was associated with this type of lens opacity.
Other forms of autosomal dominantly inherited, congenital, progressive lens opacities include congenital cerulean (115660, 601547, 608983, 610202), Volkmann type (115665), lamellar (116800), and congenital posterior polar (116600) cataracts. Due to clinical heterogeneity, it is not always possible to classify specific families based on the appearance and natural history of the lens opacities alone.
