Novel HSF4 mutation causes congenital total white cataract in a Chinese family.
OBJECTIVE
To identify the disease-causing gene (mutation) in a Chinese family affected with autosomal dominant congenital total white cataract.


METHODS
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.
Ke
Tie
T
Center for Human Genome Research and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China.
Wang
Qing K
QK
Ji
Binchu
B
Wang
Xu
X
Liu
Ping
P
Zhang
Xianqin
X
Tang
Zhaohui
Z
Ren
Xiang
X
Liu
Mugen
M
D017668:Age of Onset; D044466:Asian People / Q000208:ethnology; D002386:Cataract / Q000151:congenital / Q000208:ethnology / Q000235:genetics*; D002387:Cataract Extraction; D002648:Child; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D005819:Genetic Markers; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors