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

dc.contributor.authorAraujo, Thais Fenz
dc.contributor.authorRibeiro, Erlane Marques
dc.contributor.authorArruda, Anderson Pontes
dc.contributor.authorMoreno, Carolina Araujo
dc.contributor.authorVasconcelos de Medeiros, Paula Frassinetti
dc.contributor.authorMinillo, Renata Moldenhauer
dc.contributor.authorMelo, Debora Gusmao
dc.contributor.authorKim, Chong Ae
dc.contributor.authorRodovalho Doriqui, Maria Juliana
dc.contributor.authorFelix, Temis Maria
dc.contributor.authorFock, Rodrigo Ambrosio [UNIFESP]
dc.contributor.authorCavalcanti, Denise Pontes
dc.description.abstractBackground: 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.affiliationUniv Estadual Campinas, Fac Med Sci, Dept Med Genet, Skeletal Dysplasia Grp, Campinas, SP, Brazil
dc.description.affiliationChildrens Hosp Albert Sabin, Fortaleza, Ceara, Brazil
dc.description.affiliationMed Sci Fac Juazeiro do Norte FMJ, Juazeiro Do Norte, CE, Brazil
dc.description.affiliationUniv Estadual Campinas, Dept Med Genet, Fac Med Sci, Perinatal Genet Program, Campinas, SP, Brazil
dc.description.affiliationUniv Fed Campina Grande, Campina Grande, PB, Brazil
dc.description.affiliationChildrens Clin, City Hall Guarulhos, Guarulhos, SP, Brazil
dc.description.affiliationFed Univ Sao Carlos UFSCAR, Dept Med, Sao Carlos, SP, Brazil
dc.description.affiliationUniv Sao Paulo FCMUSP, Fac Med Sci, Childrens Inst, Med Genet Unit, Sao Paulo, SP, Brazil
dc.description.affiliationChildrens Hosp Juvencio Mattos, Sao Luis, MA, Brazil
dc.description.affiliationClin Hosp Porto Alegre, Med Genet Serv, Porto Alegre, RS, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Ctr Genet Med, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Ctr Genet Med, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCNPq [402008/2010-3, 590148/2011-7]
dc.description.sponsorshipCAPES [3300017023p6]
dc.description.sponsorshipFapesp [2015/22145-6]
dc.description.sponsorshipIDCAPES: 3300017023p6]
dc.identifier.citationEuropean Journal Of Medical Research. London, v. 21, p. -, 2016.
dc.publisherBiomed Central Ltd
dc.rightsAcesso aberto
dc.subjectCathepsin Ken
dc.subjectNovel mutationen
dc.titleMolecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast regionen