[A novel GJA8 mutation in a Chinese family with autosomal dominant congenital cataract].
OBJECTIVE
To identify the mutations in the gap junction protein alpha3/alpha8 gene (GJA3 or GJA8) in the Chinese family with autosomal dominant congenital cataract (ADCC).


METHODS
All subjects(5 family members and 100 unrelated control individuals)were undergone comprehensive ophthalmic examination, and genomic DNA was extracted from peripheral blood (5 mL). The exons and flanking introns of GJA3/GJA8 genes were amplified by polymerase chain reaction (PCR). Purified PCR products were then sequenced directly for screening disease-causing mutations.


RESULTS
Upon bidirectional sequence analysis, a G-->A transition at nucleotide 138 (c.138G>A)in exon 2 of GJA8 was found, resulting in synonymous mutation of glycine (GGG) to glycine (GGA). An additional G-->T transvertion at nucleotide 139 (c.139G>T) in exon 2 of GJA8, resulting in a missense mutation of asparagines (GAU) to tyrosine (UAU) at codon 47 (D47Y). These two alterations were not seen in all unaffected members and 100 unrelated control individuals. Bioinformatic analyses also showed that a highly conserved region was located at Asp47. Meanwhile no sequence variations for GJA3 were detected from the 3 affected members.


CONCLUSIONS
A novel disease-causing mutation (D47Y) of GJA8 gene in a Chinese family with ADCC is reported.
Lin
Ying
Y
Sichuan Academy of Medical Science & Sichuan Provincial Peoples' Hospital, Chengdu, Sichuan, 610072 People's Republic of China.
Liu
Ni-ni
NN
Lei
Chun-tao
CT
Fan
Ying-chuan
YC
Liu
Xiao-qi
XQ
Yang
Yang
Y
Wang
Jun-fang
JF
Liu
Bing
B
Yang
Zheng-lin
ZL
D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002675:Child, Preschool; D017630:Connexins / Q000737:chemistry / Q000235:genetics*; D017124:Conserved Sequence; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005190:Family; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D000099264:Connexin 50
D017630:Connexins; D005136:Eye Proteins; D000099264:Connexin 50