A novel GJA8 mutation causing a recessive triangular cataract.
OBJECTIVE
The aim of the study was to characterize the underlying mutation in a consanguineous family having cataracts.


METHODS
Family D having congenital cataracts was treated at the University Eye Clinics at Giessen (Germany). Lens material from surgeries was collected, immediately frozen at -80 degrees C, and used for cDNA production. Blood was taken from the proband and available family members. Polymerase chain reaction (PCR)-amplified DNA fragments were characterized by sequencing and restriction digestion.


RESULTS
The proband, AD, has 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. The proband's lens cDNA showed a homozygous insertion of one G after position 776 of the GJA8 gene, leading to a frame shift and 123 novel amino acids. The homozygous mutation was confirmed in the genomic DNA and is 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
The ins776G mutation most likely causes a recessive triangular cataract with variable expressivity of a weak phenotype in heterozygotes.
Schmidt
Werner
W
Center of Ophthalmology, Universities of Giessen and Marburg, Giessen, Germany.
Klopp
Norman
N
Illig
Thomas
T
Graw
Jochen
J
D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D000099264:Connexin 50
D017630:Connexins; D005136:Eye Proteins; D000099264:Connexin 50