Receive Congenital Total Cataract with Microcornea and Heterozygote Carrier ign Caued by a Novel Miene CRYAA Mutation (R54C)

Purpoe To determine the genetic bai for congenital total white cataract with microcornea in three affected ibling. Deign Propective interventional cae erie. Method Clinical ophthalmic examination, venou blood ampling for linkage analye, and diagnotic teting of identified candidate gene(). Reult Three ibling had congenital total white cataract with microcornea; the parent and even other ibling were aymptomatic. Linkage analyi mapped the phenotype to Ha 21q22.3, the region of the gene for the alpha-A component of alpha-crytallin (CRYAA), with a logarithm of odd (LOD) core of 2.5. Diagnotic CRYAA equencing revealed a novel homozygou nonene mutation (R54C) in the three affected individual only. One other ibling and the two parent were heterozygote; thee individual had punctuate lenticular opacitie evident by careful lit-lamp biomicrocopy which were not preent in the noncarrier, all of whom had unremarkable ophthalmic examination. Concluion R54C i the econd reported receive CRYAA mutation aociated with congenital cataract and the firt with decribed morphology: punctuate lenticular opacitie in carrier and congenital total white cataract with microcornea in homozygote. The microcornea may have been caued by an inductive effect on the developing cornea from the abnormal len and/or reduced CRYAA molecular chaperoning of the cornea.