title: Identification of a De Novo 3bp Deletion in CRYBA1/A3 Gene in Autosomal Dominant Congenital Cataract.
abstract: Autosomal dominant congenital cataract (ADCC) is the most common form of inherited cataracts and accounts for one-third of congenital cataracts. Heterozygous null mutations in the crystallin genes are the major cause of the ADCC. This study aims to detect the mutational spectrum of four crystallin genes, CRYBA1/A3, CRYBB1, CRYBB2 and CRYGD in an Iranian family. Genomic DNA was isolated from whole blood cells from theproband and other family members. The coding regions and flanking intronicsequences of crystalline genes were analyzed by Sanger sequencing in aproband with ADCC. The identified mutation was further evaluated in available family members. To predict the potential protein partners of CRYBA1/A3, we also used an in-silico analysis. A de novo heterozygous deletion (c.272-274delGAG, p.G91del) in exon 4 of CRYBA1/A3 gene, leading to a deletion of Glycine at codon 91 was found. This genetic variation did not change the reading frame of CRYBA1 protein. In conclusion, we identified a de novo in-frame 3-bp deletion in the proband with an autosomal dominant congenital cataract, but not in her parents, in an Iranian family. This mutation has occurred de novo on a paternal gamete during spermatogenesis. The in-silico results predicted the interaction of CRYBA1 protein with the other CRY as well as proteins responsible for eye cell signaling.
authors.affiliation: Farabi Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Mohebi
authors.affiliation: Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Akbari
authors.affiliation: Department of Molecular Cell Biology and Genetics, Bushehr Branch, Islamic Azad University, Bushehr, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Babaei
authors.affiliation: Department of Biochemistry and Genetics, Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.
authors.forename: Abdolrahim
authors.initials: A
authors.lastname: Sadeghi
authors.affiliation: Department of Molecular Cell Biology and Genetics, Bushehr Branch, Islamic Azad University, Bushehr, Iran. AND Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansour
authors.initials: M
authors.lastname: Heidari
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002386:Cataract / Q000097:blood / Q000235:genetics*; D002648:Child; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D014644:Genetic Variation; D005998:Glycine / Q000235:genetics; D006801:Humans; D007492:Iran; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010290:Parents; D010375:Pedigree; D017422:Sequence Analysis, DNA / Q000379:methods; D017384:Sequence Deletion / Q000235:genetics*; D038205:beta-Crystallin A Chain / Q000097:blood / Q000235:genetics*; D038206:beta-Crystallin B Chain / Q000097:blood / Q000235:genetics; D038222:gamma-Crystallins / Q000097:blood / Q000235:genetics
chemical_list: C489108:CRYBA1 protein, human; C105601:CRYBB1 protein, human; C504903:CRYGD protein, human; D003062:Codon; D038205:beta-Crystallin A Chain; D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2; D038222:gamma-Crystallins; D005998:Glycine
keywords: CRYBA1/3; Cataract; Directsequencing; Frameshift mutation; Truncated protein