Novel HSF4 mutation causes congenital total white cataract in a Chinese family
Novel HSF4 mutation causes congenital total white cataract in a Chinese family
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DOI：
10.1016/j.ajo.2006.03.056
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Liu, Mugen
中科院分区：
文献类型：
--
作者：
Ke, Tie;Wang, Qing K.;Liu, Mugen
目得：目的：研究一个常染色体显性遗传先天性全白色白内障家系的致病基因（突变），设计：观察性病例系列研究。方法：采用基因分型和连锁分析方法，确定该家系致病基因与编码热休克转录因子（HSFs）家族成员的HSF4基因的连锁关系。直接DNA序列分析用于鉴定致病突变。结果：中国人白内障家系的HSF4基因与标记D16S3043连锁，进一步的单倍型分析确定了HSF4位于D16S515和D16S415之间的致病基因。在HSF 4中发现了一个新的突变c.221G > A，该突变导致密码子74处高度保守的精氨酸残基被组氨酸取代（p.R74H）。R74 H突变与家系中的患病个体共分离，在未患病的家系成员和150名无关的正常对照中不存在。结论：本研究发现了一个中国人白内障家系中转录因子基因HSF 4的新错义突变R74 H，扩大了HSF 4突变导致白内障的基因谱。
PURPOSE: To identify the disease-causing gene (mutation) in a Chinese family affected with autosomal dominant congenital total white cataract.DESIGN: Observational case series.METHODS: Genotyping and linkage analyses were used to identify the linkage of the disease-causing gene in the Chinese family to the HSF4 gene encoding a member of the family of heat shock transcription factors (HSFs). Direct DNA sequence analysis was used to identify the disease-causing mutation. Polymerase chain reaction/restriction fragment length polymorphism analysis was used to demonstrate cosegregation of the HSF4 mutation with the cataract and the absence of the mutation in the normal controls.RESULTS: The cataract gene in the Chinese family was linked to marker D16S3043, and further haplotype analysis defined the causative gene between D16S515 and D16S415 within which HSF4 is located. A novel mutation c.221G > A was identified in HSF4, which results in substitution of a highly conserved arginine residue by histidine at codon 74 (p.R74H). The R74H mutation cosegregated with the affected individuals in the family and did not exist in unaffected family members and 150 unrelated normal controls.CONCLUSIONS:These results identified a novel missense mutation R74H in the transcription factor gene HSF4 in a Chinese cataract family and expand the spectrum of HSF4 mutations causing cataract.