A unique form of autosomal dominant cataract explained by gene conversion between β-crystallin B2 and its pseudogene

Editor—Using linkage analysis, a large Indian family with autosomal dominant sutural cataract and cerulean opacities was mapped to chromosome 22 and two cosegregating sequence changes (475C→T and 483C→T) were identified in the CRYBB2 gene. The first was previously described in two genetically unrelated families with other inherited forms of cataract. The two sequence alterations are identical to the sequence of the CRYBP1 pseudogene that is 228 kb apart. Furthermore, the pseudogene-like fragment within the CRYBB2 gene is flanked by chromosomal junction sequences. Therefore, we conclude that gene conversion is the most likely mechanism leading to this mutation. Alternatively, dual point mutation would explain our findings. In addition, since the three families with Q155X mutations all show different types of cataract, we conclude that mutant CRYBB2 causes cataract formation but other modifying factors determine the type of cataract. Autosomal dominant congenital cataract (ADCC) is a clinically and genetically heterogeneous group of disorders that cause blindness. More than 13 independent loci have been mapped, and 10 different genes identified so far. Five of them are crystallin genes that are categorised into the α, β, γ, μ, and ζ subgroups. The crystallins constitute the main lens proteins, whereby β-crystallin B2 is the only abundant protein in the adult lens fibre in man.1 2 Causative mutations have been recognised in the α-crystallin A gene (zonular central nuclear cataract),3 the β-crystallin A3/A1 gene (zonular cataracts with sutural opacities),4 the γ-crystallin C gene (Coppock-like cataract),5 and the γ-crystallin D gene (progressive juvenile onset punctate cataract).6These and all other ADCC mutations identified so far are private mutations, with one exception. Litt et al 7 described a nonsense mutation, Q155X, in the β-crystallin B2 gene leading to cerulean cataract. Exactly the same mutation was identified by Gill et al 8 in …