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Open Access 01-12-2016 | Research

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

Authors: Thaís Fenz Araujo, Erlane Marques Ribeiro, Anderson Pontes Arruda, Carolina Araujo Moreno, Paula Frassinetti Vasconcelos de Medeiros, Renata Moldenhauer Minillo, Débora Gusmão Melo, Chong Ae Kim, Maria Juliana Rodovalho Doriqui, Têmis Maria Felix, Rodrigo Ambrosio Fock, Denise Pontes Cavalcanti

Published in: European Journal of Medical Research | Issue 1/2016

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 Ceará 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 Ceará, 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 Ceará 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 Ceará (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 Ceará have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast.

Conclusions

The high frequency of pycnodysostosis in Ceará State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceará, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceará, suggestive of a founder effect.

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Title: Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region
Authors: Thaís Fenz Araujo
Erlane Marques Ribeiro
Anderson Pontes Arruda
Carolina Araujo Moreno
Paula Frassinetti Vasconcelos de Medeiros
Renata Moldenhauer Minillo
Débora Gusmão Melo
Chong Ae Kim
Maria Juliana Rodovalho Doriqui
Têmis Maria Felix
Rodrigo Ambrosio Fock
Denise Pontes Cavalcanti
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: European Journal of Medical Research / Issue 1/2016
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-016-0228-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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