A juvenile-onset, progressive cataract locus on chromosome 3q21-q22 is associated with a missense mutation in the beaded filament structural protein-2
A juvenile-onset, progressive cataract locus on chromosome 3q21-q22 is associated with a missense mutation in the beaded filament structural protein-2
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DOI：
10.1086/302871
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发表时间：
2000-04-01
影响因子：
9.8
通讯作者：
Gorin, MB
中科院分区：
文献类型：
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作者：
Conley, YP;Erturk, D;Gorin, MB
少年性白内障与先天性白内障的区别在于出生时晶状体最初是透明的，第二和三十年逐渐发展为晶状体混浊。分离常染色体显性遗传性少年性白内障的多世代家系的全基因组连锁分析，在染色体区域3q21.2-q22.3确定了一个基因座。由于晶状体珠状细丝结构蛋白2(BFSP2)的编码基因与该基因非常接近，我们对BFSP2的编码序列进行了突变筛查。我们观察到了一种独特的C-->；T转变，这种转变在200条正常染色体中没有观察到。我们预测，这导致了与白内障共分离的外显子4上的非保守R287W替换。这种突变改变了中间纤维中央杆状结构域中进化上保守的精氨酸残基。考虑到BFSP2在晶状体细胞骨架中的功能，这种改变很可能是我们研究的家族成员白内障的原因。这是第一个非晶体蛋白结构基因突变导致青少年发病的进行性白内障的例子。
Juvenile-onset cataracts are distinguished from congenital cataracts by the initial clarity of the lens at birth and the gradual development of lens opacity in the second and third decades of life. Genomewide linkage analysis in a multigenerational pedigree, segregating for autosomal dominant juvenile-onset cataracts, identified a locus in chromosome region 3q21.2-q22.3. Because of the proximity of the gene coding for lens beaded filament structural protein-2 (BFSP2) to this locus, we screened for mutations in the coding sequence of BFSP2. We observed a unique C-->T transition, one that was not observed in 200 normal chromosomes. We predicted that this led to a nonconservative R287W substitution in exon 4 that cosegregated with cataracts. This mutation alters an evolutionarily conserved arginine residue in the central rod domain of the intermediate filament. On consideration of the proposed function of BFSP2 in the lens cytoskeleton, it is likely that this alteration is the cause of cataracts in the members of the family we studied. This is the first example of a mutation in a noncrystallin structural gene that leads to a juvenile-onset, progressive cataract.