A novel T -> G splice site mutation of CRYBA1/A3 associated with autosomal dominant nuclear cataracts in a Chinese family

作者：Yang, Zhenfei; Su, Dongmei; Li, Qian; Yang, Fan; Ma, Zicheng; Zhu, Siquan^*; Ma, Xu

来源：Molecular Vision, 2012, 18(134-35): 1283-1288.

• CRYSTALLIN
• GENETICS
• BETA-A1-CRYSTALLIN
• PROTEIN

Purpose: The purpose of this study was to identify the disease-causing mutation and the molecular phenotype that are responsible for the presence of an autosomal dominant congenital nuclear cataract disease in a Chinese family.
Methods: The family history and clinical data were recorded. The patients were given a physical examination and their blood samples were collected for DNA extraction. Direct sequencing was used to detect the mutation. Transcription analysis of the mutant crystallin, beta A1 (CRYBA1/A3) gene was performed to verify whether the defective mutation had influenced the splice of the mature mRNA.
Results: The phenotype of the congenital cataract in the family was identified as a nuclear cataract type, by using slit-lamp photography. Direct sequencing revealed a novel mutation IVS3+2 T -> G in CRYBA1/A3. This mutation co-segregated with all affected individuals in the family, but was not found in unaffected family members nor in the 100 unrelated controls. Transcription analysis of the mutant CRYBA1/A3 gene indicated that this mutation had influenced the splice of the mature mRNA.
Conclusions: Our study identified a novel splice site mutation in CRYBA1/A3. This mutation was responsible for aberrant splicing of the mature mRNA and had caused the congenital nuclear cataracts in the family. This is the first report relating an IVS3+2 T -> G mutation of CRYBA1/A3 to congenital cataracts.

• 出版日期2012-5-15
• 单位国家卫生计生委科学技术研究所; 首都医科大学