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.
.Bronsard A, Geneau R, Shirima S, Courtright P, Mwende J. Why are children brought late for cataract surgery. Qualitative findings from Tanzania?Qualitative findings from Tanzania. Ophthalmic Epidemiol 2008;15:383-8.
Yorston D. The global initiative vision 2020: The right to sight childhood blindness. Community Eye Health 1999;12:44-5.
Gilbert C, Foster A. Childhood blindness in the context of VISION 2020-The right to Sight. Bull World Health Organ 2001;79:227-32.
Hejtmancik JF. Congenital cataracts and their molecular genetics. Semin Cell DevBiol 2008;19:134-49.
Marner E, Rosenberg T, Eiberg H. Autosomal dominant congenital cataract: morphology and genetic mapping. ActaOphthalmol (Copenh) 1989;67:151-8.
Reddy MA, Francis PJ, Berry V, Bhattacharya SS, Moore AT. Molecular genetic basis of inherited cataract and associated phenotypes. SurvOphthalmol 2004;49:300-15.
Amaya L, Taylor D, Russell-Eggitt I, Nischal KK, Lengyel D. The morphology and natural history of childhood cataracts. SurvOphthalmol 2003;48:125-44.
Sun W, Xiao X, Li Sh, Guo X, Zhang Q. Exome Sequencing of 18 Chinese Families with Congenital Cataracts: A New Sight of the NHS Gene. PLoS ONE2014;9:e100455.
Shiels A, Bennett TM, Hejtmancik JF. Cat-Map: putting cataract on the map. Mol Vis 2010;6:2007-15.
SharifiYazdi MK, Akbari A, SoltanDallal MM. Multiplex polymerase chain reaction (PCR) assay for simultaneous detection of shiga-like toxin (stx1 and stx2), intimin (eae) and invasive plasmid antigen H (ipaH) genes in diarrheagenic Escherichia coli. African Journal of Biotechnology 2011;10 (9): 1522-1526.
AkbariA, MobiniGR, MaghsoudiR, AkhtariJ, FaghihlooE, FarahnejadZ.Modulation of transforming growth factor-β signaling transducers in colon adenocarcinoma cells induced by staphylococcal enterotoxin B. Molecular medicinereports 2016;13 (1):909-914.
Lampi KJ, Shih M, Ueda Y, Shearer T, David LL. Lens Proteomics: Analysis of Rat Crystallin Sequences and Two-Dimensional Electrophoresis Map. Invest Ophthalmol Vis Sci 2002;43:216-24.
Ferrini W, Schorderet DF, Othenin-Girard P, Héon E, Munier FL. CRYBA1/3 gene mutation associated with suturesparing autosomal dominant congenital nuclear cataract: a novel phenotype. Invest Ophthalmol Vis Sci2004;45:1436-41.
Wang KJ, Li SS, Yun B, Ma WX, Jiang TG, Zhu SQ.
A novel mutation in MIP associated with congenital nuclear cataract in a Chinese family. Mol Vis 2011;17:70-7.
Klopp N, Héon E, Billingsley G, Illig T, Wjst M, Rudolph G, et al. Further genetic heterogeneity for autosomal dominant human sutural cataracts. Ophthalmic Res 2003;35:71-7.
Vanita V, Hejtmancik JF, Hennies HC, Guleria K, Nürnberg P, Singh D, et al. Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin. Mol Vis 2006;12:93-9.
Vanita V, Hennies HC, Singh D, Nürnberg P, Sperling K, Singh JR. A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin. Mol Vis 2006;12:1217-22.
Qi Y, Jia H, Huang S, Lin H, Gu J, Su H, et al. A deletion mutation in the betaA1/A3 crystallin gene (CRYBA1/A3) is associated with autosomal dominant congenital nuclear cataract in a Chinese family. Hum Genet 2004;114:192-7.
Reddy MA, Bateman OA, Chakarova C, Ferris J, Berry V, Lomas E, et al. Characterization of the G91del CRYBA1/3-crystallin protein: a cause of human inherited cataract.HumMol Genet 2004;13:945-53.
Pras E, Levy-Nissenbaum E, Bakhan T, Lahat H, Assia E, Geffen-Carmi N, et al. A missense mutation in the LIM2 gene is associated with autosomal recessive presenile cataract in an inbred Iraqi Jewish family. Am J Hum Genet 2002;70:1363-7.
Arora A, Minogue P J, Liu X, Reddy M A, Ainsworth J R, Bhattacharya SS, et al. A novel GJA8 mutation is associated with autosomal dominant lamellar pulverulent cataract: further evidence for gap junction dysfunction in human cataract. J Med Genet 2006;43:e2.
Chang B, Wang X, Hawes N L, Ojakian R, Davisson M T, Lo WK, et al. A Gja8 (Cx50) point mutation causes an alteration of alpha 3 connexin (Cx46) in semi-dominant cataracts of Lop10 mice. Hum Mol Genet 2002;11;507-13.
Okano Y, Asada M, Fujimoto A, Ohtake A, Murayama K, Hsiao KJ, et al. A genetic factor for age-related cataract: identification and characterization of a novel galactokinase variant, “Osaka,” in Asians. Am J Hum Genet 2001;68:1036-42.
Maraini G, Hejtmancik JF, Shiels A, Mackay DS, Aldigeri R, Jiao XD, et al. Galactokinase gene mutations and age-related cataract. Lack of association in an Italian population. Mol Vis 2003;9:397-400.
| Files | ||
| Issue | Vol 54, No 12 (2016) | |
| Section | Articles | |
| Keywords | ||
| Cataract CRYBA1/3 Directsequencing Frameshift mutation Truncated protein | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
