Kannabiran C, Rogan P K, Olmos L, Basti S, Rao G N, Kaiser-Kupfer M, Hejtmancik J F
National Eye Institute, NIH, Bethesda, MD 20892-1860, USA.
Mol Vis. 1998 Oct 23;4:21.
Congenital cataracts constitute a morphologically and genetically heterogeneous group of diseases that are a major cause of childhood blindness. Autosomal Dominant Zonular Cataracts with Sutural Opacities (CCZS) have been mapped to chromosome 17q11-q12 near the betaA3A1-crystallin gene (CRYBA1). The betaA3A1-crystallin gene was investigated as the causative gene for the cataracts.
The betaA3/A1-crystallin gene was sequenced in affected and control individuals. Base changes were confirmed and assayed in additional family members and controls using NlaIII restriction digestion of PCR amplified DNA sequences. Base changes were assessed for their effects on splicing by information analysis.
The cataracts are associated with a sequence change in the 5' (donor) splice site of intron 3: GC(g->a)tgagt. The sequence change also creates a new NlaIII site. This base change cosegregates with the cataracts in this family, being present in every affected individual. Conversely, this base change was not seen in 140 chromosomes examined in 70 unaffected and unrelated individuals. Information theory mutational analysis shows that the base change lowers the information content of the splice site from 6.0 to -6.8 bits, so that splicing would not be expected to occur at the altered site.
Taken together, these observations suggest that the observed mutation might be causally related to the cataracts in this family.
先天性白内障是一组形态和遗传异质性疾病，是儿童失明的主要原因。常染色体显性遗传性带状白内障伴缝合线混浊（CCZS）已被定位到17号染色体q11 - q12区域，靠近βA3A1 - 晶体蛋白基因（CRYBA1）。对βA3A1 - 晶体蛋白基因进行研究，以确定其是否为白内障的致病基因。
对患病个体和对照个体的βA3/A1 - 晶体蛋白基因进行测序。通过对PCR扩增的DNA序列进行NlaIII限制性酶切，在其他家庭成员和对照中确认并检测碱基变化。通过信息分析评估碱基变化对剪接的影响。
白内障与内含子3的5'（供体）剪接位点的序列变化有关：GC（g->a）tgagt。该序列变化还产生了一个新的NlaIII位点。这种碱基变化与该家族中的白内障共分离，存在于每个患病个体中。相反，在70名未受影响且无亲缘关系的个体所检测的140条染色体中未发现这种碱基变化。信息论突变分析表明，碱基变化使剪接位点的信息含量从6.0位降至 - 6.8位，因此预计在改变的位点不会发生剪接。
综上所述，这些观察结果表明所观察到的突变可能与该家族中的白内障有因果关系。
