Abstract
Purpose: :
Aim of the study was the characterization of underlying mutations in two cataract families.
Methods: :
Families suffering from congenital cataracts have been collected in Gießen (Germany). Lens material from surgeries was collected, immediately frozen at -80oC and used for cDNA production. Blood was taken from the probands and available family members. PCR amplified DNA fragments were characterized by sequencing and restriction digest.
Results: :
The proband LB suffers from a diffuse white lens opacity; the parents are healthy. In the cDNA coding for GJA8, a T741->G nucleotide substitution was observed (I247M amino-acid exchange); this mutation was reported previously to be causative for cataracts. Surprisingly, the same mutation was identified in the healthy mother suggesting that it has no full penetrance or is even a rather rare polymorphism than a cataract-causing mutation.The proband AD suffers from a dense, triangular nuclear cataract. The parents are consanguineous and the mother and grandmother suffer from a discrete, symmetric opacity of the fetal lens nucleus. In the proband’s lens cDNA of GJA8, a homozygous insertion of one G was observed after pos. 776 leading to a frame shift and 123 novel amino acids. The homozygous mutation was confirmed in the genomic DNA and also present in the cataract-operated brother of the proband; all other family members investigated were heterozygous. The mutation could not be detected in 96 healthy controls from Germany.
Conclusions: :
While the I247M mutation is most likely a rare polymorphism or is not fully penetrant, the ins776G mutation causes a recessive triangular cataract with variable expressivity of a weak phenotype in heterozygotes.
Keywords: cataract • genetics • gap junctions/coupling