Novel Deletion Alleles Carrying Cyp21a1p/a2 Chimeric Genes In Brazilian Patients With 21-hydroxylase Deficiency

dc.creatorCoeli F.B.
dc.creatorSoardi F.C.
dc.creatorBernardi R.D.
dc.creatorde Araujo M.
dc.creatorPaulino L.C.
dc.creatorLau I.F.
dc.creatorPetroli R.J.
dc.creatorde Lemos-Marini S.H.V.
dc.creatorBaptista M.T.M.
dc.creatorGuerra-Junior G.
dc.creatorde-Mello M.P.
dc.date2010
dc.date2015-06-26T12:37:39Z
dc.date2015-11-26T15:27:43Z
dc.date2015-06-26T12:37:39Z
dc.date2015-11-26T15:27:43Z
dc.date.accessioned2018-03-28T22:36:23Z
dc.date.available2018-03-28T22:36:23Z
dc.identifier
dc.identifierBmc Medical Genetics. , v. 11, n. 1, p. - , 2010.
dc.identifier14712350
dc.identifier10.1186/1471-2350-11-104
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-77953923768&partnerID=40&md5=543c50109a5bc358c16ffce1d5043004
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/91224
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/91224
dc.identifier2-s2.0-77953923768
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1261411
dc.descriptionBackground: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in CYP21A2 gene. The human gene is located at 6p21.3 within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module. The CYP21 extra copy is a pseudogene (CYP21A1P). In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric CYP21A1P/A2 genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular C4/CYP21 locus. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency.Methods: We used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of CYP21A1P/A2 chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with C4/CYP21 30-kb deletion were included in the study.Results: An allele carrying a CYP21A1P/A2 chimeric gene was found unusually associated to a C4B/C4A Taq I 6.4-kb fragment, generally associated to C4B and CYP21A1P deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in CYP21A1P of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different approaches revealed nine haplotypes for deleted 21-hydroxylase deficiency alleles.Conclusions: This study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying CYP21A1P/A2 chimeric genes in Brazil. © 2010 Coeli et al; licensee BioMed Central Ltd.
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dc.description1
dc.description
dc.description
dc.descriptionNew, M.I., Inborn errors of adrenal steroidogenesis (2003) Mol Cel Endocrinol, 211, pp. 75-83
dc.descriptionWhite, P.C., Speiser, P.W., Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (2000) Endocrine Reviews, 21, pp. 245-291. , 10.1210/er.21.3.245, 10857554
dc.descriptionKeegan, C.E., Killeen, A.A., An overview of molecular diagnostic of steroid 21-hydroxylase deficiency (2001) J Mol Diagnostic, 3, pp. 49-54
dc.descriptionCarroll, M.C., Campbell, R.D., Bentley, D.R., Porter, R.R., A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B (1984) Nature, 307, pp. 237-241. , 10.1038/307237a0, 6559257
dc.descriptionWhite, P.C., Grossberger, D., Onufer, B.J., Chaplin, D.D., New, M.I., Dupont, B., Strominger, J.L., Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth complement in man (1985) Proc Natl Acad Sci USA, 82, pp. 1089-1093. , 10.1073/pnas.82.4.1089, 397199, 2983330
dc.descriptionHigashi, Y., Yoshioka, H., Yamane, M., Gotoh, O., Fujii-Kuriyama, Y., Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene (1986) Proc Natl Acad Sci USA, 83, pp. 2841-2845. , 10.1073/pnas.83.9.2841, 323402, 3486422
dc.descriptionWhite, P.C., New, M.I., Dupont, B., Structure of human steroid 21-hydroxylase genes (1986) Proc Natl Acad Sci USA, 83, pp. 5111-5115. , 10.1073/pnas.83.14.5111, 323900, 3487786
dc.descriptionYang, Z., Mendoza, A.R., Welch, T.R., Zipf, W.B., Yu, C.Y., Modular variations of the human major histocompatibility complex class III genes for serine/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module). A mechanism for gene deletions and disease associations (1999) J Biol Chem, 274, pp. 12147-12156. , 10.1074/jbc.274.17.12147, 10207042
dc.descriptionDangel, A.W., Mendoza, A.R., Baker, B.J., Daniel, C.M., Carroll, M.C., Wu, L.C., Yu, C.Y., The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates (1994) Immunogenetics, 40, pp. 425-436. , 10.1007/BF00177825, 7545960
dc.descriptionTassabehji, M., Strachan, T., Anderson, M., Campbell, R.D., Collier, S., Lako, M., Identification of a novel family of human endogenous retroviruses and characterization of one family member, HERV-K(C4), located in the complement C4 gene cluster (1994) Nucleic Acids Res, 22, pp. 5211-5217. , 10.1093/nar/22.24.5211, 332062, 7816608
dc.descriptionChu, X., Rittner, C., Schneider, P.M., Length polymorphism of the human complement component C4 gene is due to an ancient retroviral integration (1995) Exp Clin Immunogenet, 12, pp. 74-81
dc.descriptionBlanchong, C.A., Zhou, B., Rupert, K.L., Chung, E.K., Jones, K.N., Sotos, J.F., Zipf, W.B., Yu Yung, C., Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules in caucasians. The load of RCCX genetic diversity on major histocompatibility complex-associated disease (2000) J Exp Med, 191, pp. 2183-2196. , 10.1084/jem.191.12.2183, 2193198, 10859342
dc.descriptionSchneider, P.M., Carroll, M.C., Alper, C.A., Rittner, C., Whitehead, A.S., Yunis, E.J., Colten, H.R., Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. Restriction fragment length polymorphisms revealing structural deletions, homoduplications, and size variants (1986) J Clin Invest, 78, pp. 650-657. , 10.1172/JCI112623, 423642, 3018042
dc.descriptionKoppens, P.F., Hoogenboezem, T., Degenhart, H.J., Duplication of the CYP21A2 gene complicates mutation analysis of steroid 21-hydroxylase deficiency: characteristics of three unusual haplotypes (2002) Hum Genet, 111, pp. 405-410. , 10.1007/s00439-002-0810-7, 12384784
dc.descriptionLee, H.H., Chimeric CYP21P/CYP21 and TNXA/TNXB genes in the RCCX module (2005) Mol Gen Met, 84, pp. 4-8
dc.descriptionCarroll, M.C., Palsdottir, A., Belt, K.T., Porter, R.R., Deletion of complement C4 and steroid 21-hydroxylase genes in the HLA class III region (1985) EMBO J, 4, pp. 2547-2552. , 554542, 2996881
dc.descriptionWerkmeister, J.W., New, M.I., Dupont, B., White, P.C., Frequent deletion and duplication of the steroid 21-hydroxylase genes (1986) Am J Hum Genet, 39, pp. 461-469. , 1683994, 3490178
dc.descriptionWhite, P.C., Vilek, A., Dupont, B., New, M.I., Characterization of frequent deletions causing steroid 21-hydroxylase deficiency (1988) Proc Natl Acad Sci USA, 85, pp. 4436-4440. , 10.1073/pnas.85.12.4436, 280444, 3260033
dc.descriptionMorel, Y., David, M., Forest, M.G., Betuel, H., Hauptman, G., Andre, J., Bertrand, J., Miller, W.L., Gene conversions and rearrangements cause discordance between inheritance of forms of 21-hydroxylase deficiency and HLA types (1989) J Clin Endocrinol Metab, 68, pp. 592-599. , 10.1210/jcem-68-3-592, 2783935
dc.descriptionDonohoue, P.A., Jospe, N., Migeon, C.J., Van Dop, C., Two distinct areas of unequal crossingover within the steroid 21-hydroxylase genes produce absence of CYP21B (1989) Genomics, 5, pp. 397-406. , 10.1016/0888-7543(89)90002-5, 2613228
dc.descriptionLee, H.H., Diversity of the CYP21P-like gene in CYP21 deficiency (2005) DNA Cell Biol, 24, pp. 1-9. , 10.1089/dna.2005.24.1, 15684714
dc.descriptionPaldosttir, A., Fossdal, R., Arnason, A., Edwards, J.H., Jennson, O., Heterogeneity of human C4 gene size, a large intron (6.6 kb) is present in all C4A genes and some C4B genes (1987) Immunogenetics, 25, pp. 299-304. , 10.1007/BF00404422, 2883116
dc.descriptionHaglund-Stengler, B., Martin Ritzén, E., Gustafsson, J., Luthman, H., Haplotypes of the steroid 21-hydroxylase gene region encoding mild steroid 21-hydroxylase deficiency (1991) Proc Natl Acad Sci USA, 88, pp. 8352-8356. , 10.1073/pnas.88.19.8352, 52506, 1924294
dc.descriptionTorresani, T., Biason-Lauber, A., Congenital adrenal hyperplasia: diagnostic advances (2007) J Inherit Metab Dis, 30, pp. 563-575. , 10.1007/s10545-007-0696-6, 17694353
dc.descriptionLee, H.H., Chang, J.G., Tsai, C.H., Tsai, F.J., Chao, H.T., Chung, B., Analysis of the chimeric CYP21P/CYP21 gene in steroid 21-hydroxylase deficiency (2000) Clin Chem, 46, pp. 606-611
dc.descriptionLee, H.H., Niu, D.M., Lin, R.W., Chan, P., Lin, C.Y., Structural analysis of the chimeric CYP21P/CYP21 gene in steroid 21-hydroxylase deficiency (2002) J Hum Genet, 47, pp. 517-522. , 10.1007/s100380200077, 12376740
dc.descriptionFriães, A., Rêgo, A.T., Aragüés, J.M., Moura, L.F., Mirante, A., Mascarenhas, M.R., Kay, T.T., Gonçalves, J., CYP21A2 mutations in Portuguese patients with congenital adrenal hyperplasia: identification of two novel mutations and characterization of four different partial gene conversions (2006) Mol Genet Metab, 88, pp. 58-65. , 10.1016/j.ymgme.2005.11.015, 16427797
dc.descriptionConcolino, P., Mello, E., Minucci, A., Giardina, E., Zuppi, C., Toscano, V., Capoluongo, E., A new CYP21A1P/CYP21A2 chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form (2009) BMC Med Genet, 22, pp. 10-72
dc.descriptionDe Araujo, M., Sanches, M.R., Suzuki, L.A., Guerra, G., Farah, S.B., De Mello, M.P., Molecular Analysis of CYP21 and C4 Genes in Brazilian Families the Classical Congenital Adrenal Hyperplasia (1996) Brazilian J Med Biol Res, 29, pp. 1-13
dc.descriptionBachega, T.A., Billerbeck, A.E., Madureira, G., Arnhold, I.J., Medeiros, M.A., Marcondes, J.A., Longui, C.A., Mendonca, B.B., Low frequency of CYP2B deletions in Brazilian patients with congenital adrenal hyperplasia due to 21-hydroxylas deficiency (1999) Hum Hered, 49, pp. 9-14. , 10.1159/000022833, 10189236
dc.descriptionSambrook, J., Fritsch, E.F., Maniatis, T.E., Molecular cloning, a laboratory manual (1989), New York: Cold Spring HarborWilson, R.C., Wei, J.Q., Cheng, K.C., Mercado, A.B., New, M.I., Rapid deoxyribonucleic acid analysis by allele-specific polymerase chain raction for detection of mutations in the 21-hydroxylase gene (1995) J Clin Endocrinol Metab, 80, pp. 1635-1640. , 10.1210/jc.80.5.1635, 7745011
dc.descriptionMRC-Holland - SALSA MLPA kit P050 CAH http://www.mrc-holland.com/WebForms/WebFormProductDetails.aspx?Tag=tz2fAPIAupLo0TRBqtiGHA||&ProductOID=dVNA4DAAaOA|Taylor, C.F., Charlton, R.S., Burn, J., Sheridan, E., Taylor, G.R., Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA (2003) Hum Mutat, 22, pp. 428-433. , 10.1002/humu.10291, 14635101
dc.descriptionParajes, S., Quinterio, C., Domínguez, F., Loidi, L., A simple and robust quantitative PCR assay to determine CYP21A2 gene dose in the diagnosis of 21-hydroxylase deficiency (2007) Clin Chem, 53, pp. 1577-1584. , 10.1373/clinchem.2007.087361, 17634211
dc.descriptionSzilagyi, A., Blasko, B., Szilassy, D., Fust, G., Sasvari-Szekely, M., Ronai, Z., Real-time PCR quantification of human complement C4A and C4B genes (2006) BMC Genet, 10, p. 1
dc.descriptionKleinle, S., Lang, R., Fischer, G.F., Vierhapper, H., Waldhauser, F., Födinger, M., Baumgartner-Parzer, S.M., Duplications of the functional CYP21A2 gene are primarily restricted to Q318X alleles: evidence for a founder effect (2009) J Clin Endocrinol Metab, 94, pp. 3954-3958. , 10.1210/jc.2009-0487, 19773403
dc.descriptionKoppens, P.F., Hoogenboezem, T., Degenhart, H.J., A rare TaqI polymorphism in a human complement C4 gene is caused by an additional restriction site in the first intron (1992) Immunol Lett, 34, pp. 93-97. , 10.1016/0165-2478(92)90233-E, 1362564
dc.descriptionKharrat, M., Tardy, V., M'Rad, R., Maazoul, F., Jemaa, L.B., Refaï, M., Morel, Y., Chaabouni, H., Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation (2004) J Clin Endocrinol Metab, 89, pp. 368-374. , 10.1210/jc.2003-031056, 14715874
dc.descriptionKoppens, P.F., Hoogenboezem, T., Degenhart, H.J., CYP21 and CYP21P variability in steroid 21-hydroxylase deficiency patients and in the general population in the Netherlands (2000) Eur J Hum Genet, 8, pp. 827-836. , 10.1038/sj.ejhg.5200543, 11093272
dc.descriptionSinnott, P., Collier, S., Costigan, C., Dyer, P.A., Harris, R., Strachan, T., Genesis by meiotic unequal crossover of a de novo deletion that contributes to steroid 21-hydroxylase deficiency (1990) Proc Natl Acad Sci USA, 87, pp. 2107-2111. , 10.1073/pnas.87.6.2107, 53635, 2315306
dc.descriptionGuerra-Junior, G., Grumach, A.S., Lemos-Marini, S.H., Kirschfink, M., Condino Neto, A., de Araujo, M., De Mello, M.P., Complement 4 phenotypes and genotypes in Brazilian patients with classical 21-hydroxylase deficiency (2009) Clin Exp Immunol, 155, pp. 182-188. , 10.1111/j.1365-2249.2008.03838.x, 2675248, 19137635
dc.descriptionDodds, A.W., Ren, X.D., Willis, A.C., Law, S.K., The reaction mechanism of the internal thioester in the human complement component C4 (1996) Nature, 379, pp. 177-179. , 10.1038/379177a0, 8538770
dc.descriptionDonohoue, P.A., Guethlein, L., Collins, M.M., Van Dop, C., Migeon, C.J., Bias, W.B., Schmeckpeper, B.J., The HLA-A3, Cw6,B47,DR7 extended haplotypes in salt losing 21-hydroxylase deficiency and in the Old Order Amish: identical class I antigens and class II alleles with at least two crossover sites in the class III region (1995) Tissue Antigens, 46, pp. 163-172. , 10.1111/j.1399-0039.1995.tb03115.x, 8525475
dc.descriptionChung, E.K., Yang, Y., Rennebohm, R.M., Lokki, M.L., Higgins, G.C., Jones, K.N., Zhou, B., Yu, C.Y., Genetic sophistication of human complement components C4A and C4B and RP-C4-CYP21-TNX (RCCX) modules in the major histocompatibility complex (2002) Am J Hum Genet, 71, pp. 823-837. , 10.1086/342777, 378539, 12226794
dc.descriptionChu, X., Braun-Heimer, L., Rittner, C., Schneider, P.M., Identification of the recombination site within the steroid 21-hydroxylase gene (CYP21) of the HLA B47,DR7 haplotype (1992) Exp Clin Immunogenet, 9, pp. 80-85
dc.descriptionL'Allemand, D., Tardy, V., Grüters, A., Schnabel, D., Krude, H., Morel, Y., How a patient homozygous for a 30-kb deletion of the C4-CYP 21 genomic region can have a nonclassic form of 21-hydroxylase deficiency (2000) J Clin Endocrinol Metab, 85, pp. 4562-4567. , 10.1210/jc.85.12.4562, 11134109
dc.descriptionFasano, M.B., Winkelstein, J.A., LaRosa, T., Bias, W.B., McLean, R.H., A unique recombination event resulting in a C4A*Q0,C4B*Q0 double null haplotype (1992) J Clin Invest, 90, pp. 1180-1184. , 10.1172/JCI115978, 443157, 1401055
dc.descriptionKoppens, P., Smeets, H., de Wijs, I.J., Degenhart, H., Mapping of a de novo unequal crossover causing a deletion of the steroid 21-hydroxylase (CYP21A2) gene and a non-functional hybrid tenascin-X (TNXB) gene (2003) J Med Genet, 40, pp. e53. , 10.1136/jmg.40.5.e53, 1735462, 12746407
dc.descriptionSoardi, F.C., Barbaro, M., Lau, I.F., Lemos-Marini, S.H., Baptista, M.T., Guerra-Junior, G., Wedell, A., de Mello, M.P., Inhibition of CYP21A2 enzyme activity caused by novel missense mutations identified in Brazilian and Scandinavian patients (2008) J Clin Endocrinol Metab, 93, pp. 2416-2420. , 10.1210/jc.2007-2594, 18381579
dc.descriptionMenassa, R., Tardy, V., Despert, F., Bouvattier-Morel, C., Brossier, J.P., Cartigny, M., Morel, Y., P.H62L, a rare mutation of the CYP21 gene identified in two forms of 21-hydroxylase deficiency (2008) J Clin Endocrinol Metab, 93, pp. 1901-1908. , 10.1210/jc.2007-2701, 18319307
dc.descriptionFigueiredo, M.S., Kerbauy, J., Goncalves, M.S., Arruda, V.R., Saad, S.T., Sonati, M.F., Stoming, T., Costa, F.F., Effect of ?-Thalassemia and ?-Globin Gene Cluster Haplotypes on the Hematological and Clinical Features of Sickle Anemia in Brazil (1996) Am J Hematol, 53, pp. 72-76. , 10.1002/(SICI)1096-8652(199610)53:2<72::AID-AJH3>3.0.CO;2-0, 8892730
dc.descriptionKilleen, A.A., Sane, K.S., Orr, H.T., Molecular and endocrine characterization of a mutation involving a recombination between the steroid 21-hydroxylase functional gene and pseudogene (1991) J Steroid Biochem Mol Biol, 38, pp. 677-686. , 10.1016/0960-0760(91)90078-J, 1905948
dc.descriptionKyllo, J.H., Collins, M.M., Donohoue, P.A., Constitutive human steroid 21-hydroxylase promoter gene and pseudogene activity in steroidogenic and nonsteroidogenic cells with the luciferase gene as a reporter (1995) Endocr Res, 21, pp. 777-791
dc.descriptionSørensen, K.M., Andersen, P.S., Larsen, L.A., Schwartz, M., Schouten, J.P., Nygren, A.O., Multiplex Ligation-Dependent Probe Amplification Technique for Copy Number Analysis on Small Amounts of DNA Material (2008) Anal Chem, 80, pp. 9363-9368. , 10.1021/ac801688c, 19551952
dc.languageen
dc.publisher
dc.relationBMC Medical Genetics
dc.rightsfechado
dc.sourceScopus
dc.titleNovel Deletion Alleles Carrying Cyp21a1p/a2 Chimeric Genes In Brazilian Patients With 21-hydroxylase Deficiency
dc.typeArtículos de revistas


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