Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region

Show simple item record Araujo, Thais Fenz Ribeiro, Erlane Marques Arruda, Anderson Pontes Moreno, Carolina Araujo Vasconcelos de Medeiros, Paula Frassinetti Minillo, Renata Moldenhauer Melo, Debora Gusmao Kim, Chong Ae Rodovalho Doriqui, Maria Juliana Felix, Temis Maria Fock, Rodrigo Ambrosio [UNIFESP] Cavalcanti, Denise Pontes 2019-07-22T15:46:54Z 2019-07-22T15:46:54Z 2016
dc.identifier.citation European Journal Of Medical Research. London, v. 21, p. -, 2016.
dc.identifier.issn 0949-2321
dc.description.abstract Background: Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceara State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis. Methods: The CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceara, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents. Results: We have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceara State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceara (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceara have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast. Conclusions: The high frequency of pycnodysostosis in Ceara State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceara, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceara, suggestive of a founder effect. en
dc.description.sponsorship CNPq [402008/2010-3, 590148/2011-7]
dc.description.sponsorship CAPES [3300017023p6]
dc.description.sponsorship Fapesp [2015/22145-6]
dc.format.extent -
dc.language.iso eng
dc.publisher Biomed Central Ltd
dc.rights Acesso aberto
dc.subject Pycnodysostosis en
dc.subject Cathepsin K en
dc.subject Inbreeding en
dc.subject Novel mutation en
dc.title Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region en
dc.type Artigo
dc.description.affiliation Univ Estadual Campinas, Fac Med Sci, Dept Med Genet, Skeletal Dysplasia Grp, Campinas, SP, Brazil
dc.description.affiliation Childrens Hosp Albert Sabin, Fortaleza, Ceara, Brazil
dc.description.affiliation Med Sci Fac Juazeiro do Norte FMJ, Juazeiro Do Norte, CE, Brazil
dc.description.affiliation Univ Estadual Campinas, Dept Med Genet, Fac Med Sci, Perinatal Genet Program, Campinas, SP, Brazil
dc.description.affiliation Univ Fed Campina Grande, Campina Grande, PB, Brazil
dc.description.affiliation Childrens Clin, City Hall Guarulhos, Guarulhos, SP, Brazil
dc.description.affiliation Fed Univ Sao Carlos UFSCAR, Dept Med, Sao Carlos, SP, Brazil
dc.description.affiliation Univ Sao Paulo FCMUSP, Fac Med Sci, Childrens Inst, Med Genet Unit, Sao Paulo, SP, Brazil
dc.description.affiliation Childrens Hosp Juvencio Mattos, Sao Luis, MA, Brazil
dc.description.affiliation Clin Hosp Porto Alegre, Med Genet Serv, Porto Alegre, RS, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Ctr Genet Med, Sao Paulo, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Ctr Genet Med, Sao Paulo, SP, Brazil
dc.description.sponsorshipID CNPq:402008/2010-3
dc.description.sponsorshipID 590148/2011-7
dc.description.sponsorshipID CAPES: 3300017023p6]
dc.description.sponsorshipID FAPESP:2015/22145-6
dc.identifier.file WOS000381782800001.pdf
dc.identifier.doi 10.1186/s40001-016-0228-7
dc.description.source Web of Science
dc.identifier.wos WOS:000381782800001


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