A novel p.Glu75Lys mutation in CRYBB1 with low penetrance in an Indian family with nuclear form of congenital cataract

作者：Kumar Manoj; Khokhar Sudarshan; Kaur Punit; Agarwal Tushar; Dada Rima^*

来源：Journal of the Anatomical Society of India, 2014, 63(2): 172-178.

DOI：10.1016/j.jasi.2014.11.005

• Congenital cataract
• Beta Crystallin B1
• Autosomal dominant

Introduction: To screen CRYAA, CRYAB, CRYGC, CRYGD, CRYGS, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, BFSP1, GJA3, GJA8 and HSF4 gene in an Indian family having congenital cataract.
Methods: The congenital cataract family presented at Dr. R.P. Centre for Ophthalmic Sciences, a tertiary research and referral hospital (AIIMS, New Delhi, India). CRYAA, CRYAB, CRYGC, CRYGD, CRYGS, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, BFSP1, GJA3, GJA8 and HSF4 genes were amplified. Protein structure differences analysis was performed using Discovery Studio (DS) 2.0.
Results: A three-generation Indian family with diagnosis of congenital cataract presented with bilateral dense nuclear opacities in the affected individuals. Direct sequencing analysis of 14 genes identified a novel and pathogenic nucleotide variation p.E75K in CRYBB1 gene. The mutation p.Glu75Lys alters the environment and charge on the protein surface, disrupting ionic interaction between Glu75 and Arg60. Thus p.Glu75Lys changes the electrostatic potential of the protein surface which could affect the interactions with other interacting partner proteins.
Discussions: In this case a novel heterozygous p.Glu75Lys mutation in CRYBB1 was detected in an Indian family with nuclear cataract. The mutation was inherited in autosomal dominant pattern and showed reduced penetrance. Identification and characterization of this mutation further confirm the importance of protein interactions in maintaining lens transparency, and provides insight into the molecular mechanism underlying the pathogenesis of human congenital cataract.

• 出版日期2014-12
• 单位河北医科大学