Investigation of Four Genes Responsible for Autosomal Recessive Congenital Cataract and Highly Expressed in the Brain in Four Unrelated Tunisian Families

Manèl Chograni, Myriam Chaabouni, Faouzi Maazoul, Habiba Chaabouni Bouhamed

Charles Nicolle hospital, Congenital and Hereditary Disorders Department, Tunis, Tunisia.
University Tunis Elmanar Faculté de Médecine de Tunis, Laboratoire Génétique Humaine, Tunis, Tunisia.

DOI: 10.4236/ojoph.2012.23014                

Abstract

Purpose: To identify the causative gene for phenotypes associating autosomal recessive congenital cataract, mental retardation and congenital cataract, mental retardation and microcephaly in four unrelated Tunisian families. Methods: Four genes (EPHA2, GALK1, GCNT2, and CRYBB1) were selected based on expression in human brain and their known or putative function. Linkage analyses were performed for the four genes in multiple affected and unaffected families’ members and results were explored by the GeneMapper ID v3.2 software. Results: No linkage was identified for the four studied genes in the four families. Affected members of each family did not share common haplotypes in corresponding candidate regions containing selected gene. Conclusion: Although the four studied genes were reported responsible for autosomal recessive congenital cataract and highly expressed in the human brain, we report no linkage for EPHA2, GALK1, GCNT2, and CRYBB1 genes in four families with congenital cataract, mental retardation and congenital cataract, mental retardation and microcephaly.

Keywords

Congenital Cataract; Mental Retardation; Microcephaly; Autosomal Recessive; Association; Linkage Study

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. Graw, "Congenital hereditary cataracts", Int J Dev Biol, Vol. 48, 2004, pp. 1031–1044.
[2]	J. F. Hejtmancik, N. Smaoui, "Molecular genetics of cataract", Dev Ophthalmol, Vol. 37, 2004, pp. 67-82.
[3]	A. Foster, G. J. Johnson, "Magnitude and causes of blindness in the developing world" Int Ophthalmol, No. 3, Vol. 14, 1990, pp. 135–140.
[4]	S. P. Ponnam, K. Ramesha, S. Tejwani, B. Ramamurthy, C. Kannabiran, "Mutation of the gap junction protein alpha 8 (GJA8) gene causes autosomal recessive cataract", J Med Genet, Vol. 44, No. 7, 2007, pp. e85.
[5]	E. Pras, J. Raz, V. Yahalom, M. Frydman, H. J. Garzozi, E. Pras, J. F. Hejtmancik, "A nonsense mutation in the glucosaminyl (Nacetyl) transferase 2 gene (GCNT2) association with autosomal recessive congenital cat-aracts", Invest Ophthalmol Vis Sci, , Vol. 45, No. 62004, pp. 1940-5.
[6]	N. Smaoui, O. Beltaief, S. BenHamed, R. M'Rad, F. Maazoul, A. Ouertani, H. Chaabouni, J. F. Hejtmancik, "A homozygous splice mutation in the HSF4 gene is associated with an autosomal recessive congenital cataract", Invest Ophthalmol Vis Sci, Vol. 45, No. 8, 2004, pp. 2716-21.
[7]	E. Pras, E. Levy-Nissenbaum, T. Bakhan, H. Lahat, E. Assia, N. Geffen-Carmi, M. Frydman, B. Goldman, E. Pras, "A missense mutation in the LIM2 gene is associated with autosomal recessive presenile cataract in an inbred Iraqi Jewish family", Am J Hum Genet, Vol. 70, No. 5, 2002, pp. 1363-7.
[8]	E. Pras, M. Frydman, E. Levy-Nissenbaum, T. Bakhan, J. Raz, E. I. Assia, B. Goldman, E. Pras, "A nonsense mutation (W9X) in CRYAA causes autosomal recessive cataract in an inbred Jewish Persian family", Invest Ophthalmol Vis Sci, Vol. 41, No. 11, 2000, pp. 3511-5.
[9]	R. D. Ramachandran, V. Perumalsamy, J. F. Hejtmancik, "Autosomal recessive juvenile onset cataract associated with mutation in BFSP1", Hum Genet, Vol. 121, No. 3-4, 2007, pp. 475-82.
[10]	S. A. Riazuddin, A. Yasmeen, W. Yao, Y. V. Sergeev, Q. Zhang, F. Zulfiqar, A. Riaz, S. Riazuddin, J. F. Hejtmancik, "Mutations in betaB3-crystallin associated with autosomal recessive cataract in two Pakistani families", Invest Ophthalmol Vis Sci, Vol. 46, No. 6, 2005, pp. 2100-6.
[11]	D. Cohen, U. Bar-Yosef, J. Levy, L. Gradstein, N. Belfair, R. Ofir, S. Joshua, T. Lifshitz, R. Carmi, O. S. Birk, "Homozygous CRYBB1 deletion mutation underlies autosomal recessive congenital cataract", Invest Ophthalmol Vis Sci, Vol. 48, No. 5, 2007, pp. 2208-13.
[12]	H. Kaul, S. A. Riazuddin, M. Shahid, S. Kousar, N. H. Butt, A. U. Zafar, S. N. Khan, T. Husnain, J. Akram, J. F. Hejtmancik, S. Riazuddin, "Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family", Mol Vis, Vol. 16, 2010, pp. 511-7.
[13]	A. Yasmeen, S. A. Riazuddin, H. Kaul, S. Mohsin, M. Khan, Z. A. Qazi, I. A. Nasir, A. U. Zafar, S. N. Khan, T. Husnain, J. Akram, J. F. Hejtmancik, S. Riazuddin, "Autosomal recessive congenital cataract in consanguineous Pakistani families is associated with mutations in GALK1", Mol Vis, Vol. 16, 2010, pp. 682-8.
[14]	A. Shiels, T. M. Bennett, H. L. Knopf, G. Maraini, A. Li, X. Jiao, J. F. Hejtmancik, "The EPHA2 gene is associated with cataracts linked to chromosome 1p", Mol Vis, Vol. 14, 2008, pp. 2042-55.
[15]	J. C. Ruiz, E. J. Robertson, "The expression of the receptor-protein tyrosine kinase gene, eck, is highly restricted during early mouse development", Mech Dev, Vol. 46, No. 2, 1994, pp. 87–100.
[16]	T. Mori, A. Wanaka, A. Taguchi, K. Matsumoto, M. Tohyama, "Differential expressions of the eph family of receptor tyrosine kinase genes (sek, elk, eck) in the developing nervous system of the mouse", Mol Brain Res, Vol. 29, No. 2, 1995, pp. 325–335.
[17]	D. Stambolian, Y. Ai, D. Sidjanin, K. Nesburn, G. Sathe, M. Rosenberg, D. J. Bergsma, "Cloning of the galactokinase cDNA and identification of mutations in two families with cataracts", Nat Genet, Vol. 10, No. 3, 1995, pp. 307-12.
[18]	K. Sasaki, K. Kurata-Miura, M. Ujita, K. Angata, S. Nakagawa, S. Sekine, T. Nishi, M. Fukuda, "Expression cloning of cDNA encoding a human beta-1,3-N-acetyl glucosaminyl transferase that is essential for poly-N-acetyllactosamine synthesis", Proc Natl Acad Sci, Vol. 94, No. 26, 1997, pp. 14294-9.
[19]	L. Fu, J. J. Liang, "Alteration of protein-protein interactions of congenital cataract crystalline mutants", Invest Ophthalmol Vis Sci, Vol. 44, No. 33, 2003, pp. 1155–1159.
[20]	D. S. Mackay, O. B. Boskovska, H. L. Knopf, K. J. Lampi, A. Shiels, "A nonsense mutation in CRYBB1 associated with autosomal dominant cataract linked to human chromosome 22q", Am J Hum Genet, Vol. 71, No. 5, 2002, pp. 1216–1221.
[21]	[21] E. Meyer, F. Rahman, J. Owens, S. Pasha, N. V. Morgan, R. C. Trembath, E. M. Stone, A. T. Moore, E. R. Maher, "Initiation codon mutation in betaB1-crystallin (CRYBB1) associated with autosomal recessive nuclear pulverulent cataract", Mol Vis, Vol. 15, 2009, pp. 1014-9.
[22]	H. Eiberg, A. M. Lund, M. Warburg, T. Rosen-berg, "Assignment of congenital cataract Volkmann type (CCV) to chromosome 1p36", Hum Genet, Vol. 96, No. 1, 1995, pp. 33-8.
[23]	A. C. Ionides, V. Berry, D. S. Mackay, A. T. Moore, S. S. Bhattacharya, A. Shiels, "A locus for autosomal dominant posterior polar cataract on chromosome 1p", Hum Mol Genet, Vol. 6, No. 1, 1997, pp. 47-51.
[24]	W. He, S. Li, "Congenital cataract: gene mapping", Hum Genet, Vol. 106, No. 1, 2000, pp. 1-13.
[25]	W. He, C. M. Tuck-Muller, J. E. Martínez, S. Li, E. R. Rowley, W. Wertelecki, "Molecular cha-racterization of a ring chromosome 16 from a patient with bila-teral cataracts", Am J Med Genet, Vol. 107, No. 1, 2002, pp. 12-7.
[26]	P. Finelli, P. Cavalli, D. Giardino, Gottardi G, F. Natacci, S. Savasta, L. Larizza, "FISH characterization of a supernumerary r(1)(::cen-->q22::q22-->sq21::) chromosome associated with multiple anomalies and bilateral cataracts", Am J Med Genet, Vol. 104, No. 2, 2001, pp. 157-64.
[27]	D. Dilli, S. S. Oguz, U. Dilmen, E. S. Cakar, Z. O. Tunay, O. Tok, M. A. Acar, "Congenital cataract with de novo balanced reciprocal t(3;13) (q23;q12) translocation in a newborn", J Perinat Med, Vol. 37, No. 6, 2009, pp. 717-9.
[28]	N. I. Herath, M. D. Spanevello, S. Sabesan, T. Newton, M. Cummings, S. Duffy, D. Lincoln, G. Boyle, P. G. Parsons, A. W. Boyd, "Over-expression of Eph and ephrin genes in advanced ovarian cancer: ephrin gene expression correlates with shortened survival", BMC Cancer, Vol. 6, No. , 2006, pp. 144.
[29]	G. Jun, H. Guo, B. E. Klein, R. Klein, J. J. Wang, P. Mitchell, H. Miao, K. E. Lee, T. Joshi, M. Buck, P. Chugha, D. Bardenstein, A. P. Klein, J. E. Bailey-Wilson, X. Gong, T. D. Spector, T. Andrew, C. J. Hammond, R. C. Elston, S. K. Iyengar, B. Wang, "EPHA2 is associated with age-related cortical cataract in mice and humans", PLoS Genet, Vol. 5, No. 7, 2009, pp. e1000584.
[30]	Y. S. Shin-Buehring, L. Stuempfig, E. Pouget, P. Rahm, J. Schaub, "Characterization of galactose-1-phosphate uridyl-transferase and galactokinase in human organs from the fetus and adult", Clin Chim Acta, Vol. 112, No. 3, 1981, pp. 257-65.
[31]	L. C. Yu, Y. C. Twu, M. L. Chou, M. E. Reid, A. R. Gray, J. M. Moulds, C. Y. Chang, M. Lin, "The molecular genetics of the human I locus and molecular background explain the partial association of the adult i phenotype with congenital cataracts", Blood, Vol. 101, No. 6, 2003, pp. 2081–2088.
[32]	N. Inaba, T. Hiruma, A. Togayachi, H. Iwasaki, X. H. Wang, Y. Furukawa, R. Sumi, T. Kudo, K. Fujimura, T. Iwai, M. Gotoh, M. Nakamura, H. Narimatsu, "A novel I-branching beta-1,6-N acetyl glucosaminyl transferase involved in human blood group I antigen expression", Blood, Vol. 101, No. 7, 2003, pp. 2870–2876.
[33]	B. Z. Ring, S. P. Cordes, P. A. Overbeek, G. S. Barsh, "Regulation of mouse lens fiber cell development and differentiation by the Maf gene", Development, Vol. 127, No. 2, 2000, pp. 307–317.
[34]	J. Graw, "The crystallins: genes, proteins and diseases", Biol Chem, Vol. 378, No. 11, 1997, pp. 1331–1348.
[35]	W. Hoehenwarter, J. Klose, P. R. Jungblut, "Eye lens proteomics", Amino Acids, Vol. 30, No. 4, 2006, pp. 369–389.
[36]	C. E. Willoughby, A. Shafiq, W. Ferrini, L. L. Chan, G. Billingsley, M. Priston, C. Mok, A. Chandna, S. Kaye, E. Héon, "CRYBB1 mutation associated with congenital cataract and microcornea", Mol Vis, Vol. 11, 2005, pp. 587-93.
[37]	J. Wang, X. Ma, F. Gu, N. P. Liu, X. L. Hao, K. J. Wang, N. L. Wang, S. Q. Zhu, "A missense mutation S228P in the CRYBB1 gene causes autosomal dominant congenital cataract", Chin Med J, Vol. 120, No. 9, 2007, pp. 820-4.
[38]	J. Yang, Y. Zhu, F. Gu, X. He, Z. Cao, X. Li, Y. Tong, X. Ma, "A novel nonsense mutation in CRYBB1 associated with autosomal dominant congenital cataract", Mol Vis, Vol. 14,2008, pp. 727-31.
[39]	J. Graw, "Genetics of crystallins: cataract and beyond", Exp Eye Res, Vol. 88, No. 2, 2009, pp. 173-89.