PDF(Pubmed)
Abstract：
This study was designed to identify the pathogenic variants in five Ukrainian families with autosomal dominant congenital cataracts. Cataracts can be defined broadly as any opacity of the crystalline lens. Lens development is orchestrated by transcription factors. Disease-causing variants in transcription factors and their developmental target genes, including the lens crystallins, are associated with congenital cataracts and other eye diseases. Whole-exome sequencing identified heterozygous disease-causing variants in five Ukrainian families with autosomal dominant congenital cataracts and cosegregation with cataracts was confirmed using Sanger sequencing. Family 97001 showed a missense variant (c.341T>A: p.L114Q) in HSF4; family 97003 showed a missense variant (c.53A>T: p.N18I) in CRYGA; family 97004 showed a missense variant (c. 82G>A: p.V28M) in GJA3; family 97006 showed a missense variant (c.83C>T: p. P28L) in CRYGC; and family 97008 showed a single-base insertion resulting in a frameshift (c.443_444insA: p. Met148IfsTer51) in PAX6. All five families are associated with congenital cataracts. Overall, we report four novel mutations in HSF4, CRYGA, CRYGC and PAX6, and one previously reported mutation in GJA3 that cause autosomal dominant congenital cataracts.
摘要：
这项研究旨在鉴定五个乌克兰常染色体显性先天性白内障家庭的致病变异。白内障可以广义地定义为晶状体的任何不透明性。晶状体的发育是由转录因子协调的。转录因子及其发育靶基因的致病变异,包括晶状体晶体蛋白，与先天性白内障和其他眼病有关。全外显子组测序在五个患有常染色体显性先天性白内障和白内障的乌克兰家庭中鉴定了杂合子致病变异，并使用Sanger测序确认了与白内障的共隔离。家族97001在HSF4中显示错义变体（c.341T>A：p.L114Q）；家族97003在CRYGA中显示错义变体（c.53A>T：p.N18I）；家族97004显示错义变体（c.GJA3中的82G>A：p.V28M）；家族97006在CRYGC中显示出错义变体（c.83C>T：p。P28L）；家族97008在PAX6中显示出单碱基插入，导致移码（c.443_444insA：p。Met148IfsTer51）。所有五个家庭都与先天性白内障有关。总的来说,我们报告了HSF4，CRYGA，CRYGC和PAX6，以及先前报道的GJA3突变导致常染色体显性先天性白内障。
