Contribution to the clinical and etiological study of the skeletal dysplasias and dysostosis in Brazil

• Grant number: 15/22145-6
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2016
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Denise Pontes Cavalcanti
• Grantee: Denise Pontes Cavalcanti
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The skeletal dysplasias or osteochondrodysplasias (OCD) are a heterogenous group of genetic conditions with high morbimortality that produce important changes in the growth and development of the skeletal system. In general, these conditions lead to short stature and several of them, also present important joint and spine alterations. In addition to the task of classifying and delineating new OCD and dysostosis phenotypes, in the last 25 years we have assisted the fantastic evolution in the identification of the molecular basis of these conditions. Because of the quickness of these molecular discoveries, currently more than 60% of the OCD are associated with mutation in known genes. In spite of the improvement regarding the knowledge of the OCD molecular basis, many conditions still need to be etiologically identified. In addition, novel conditions continue to be recognized. From the accumulated experience in the last years the local group is in position to increasing the investigation regarding the OCD. Therefore, the goal of the present investigation is to introducing the new genetic technologies like the next generation sequencing (NGS) to the investigation of the OCD and dysostosis, trying to identify the molecular bases of these conditions. Likewise, this study aims to exploring the genotype-phenotype correlation among the still poorly characterized OCD and dysostosis. Finally, the results of the present study can help us to outline, at least partially, the OCD clusters in Brazil. (AU)

Scientific publications

(17)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DI LORENZO, GIORGIA; WESTERMANN, LENA M.; YORGAN, TIMUR A.; STUERZNICKEL, JULIAN; LUDWIG, NATANIEL F.; AMMER, LUISE S.; BARANOWSKY, ANKE; AHMADI, SHIVA; POURBARKHORDARIESFANDABADI, ELHAM; BREYER, SANDRA R.; et al. Pathogenic variants in GNPTAB and GNPTG encoding distinct subunits of GlcNAc-1-phosphotransferase differentially impact bone resorption in patients with mucolipidosis type II and III. Genetics in Medicine, v. 23, n. 12, AUG 2021. (15/22145-6)

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; et al. Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region. EUROPEAN JOURNAL OF MEDICAL RESEARCH, v. 21, AUG 24 2016. (15/22145-6)

CAVALCANTI, D. P.; KANAZAWA, T. Y.; SILVEIRA, K. C.; SILVEIRA, C.; MORENO, C. A.; LACARRUBBA, M. J.; SANSEVERINO, M.; BONADIA, L. C.. Lethal skeletal dysplasias: molecular investigation in a series of 62 fetus, including a novel phenotype. European Journal of Human Genetics, v. 26, p. 1-pg., 2018-10-01. (15/22145-6)

MEDINA, CRISTINA T. N.; SANDOVAL, RENATA; OLIVEIRA, GABRIELA; SILVEIRA, KARINA DA COSTA; CAVALCANTI, DENISE P.; POGUE, ROBERT. Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v. 182, n. 4, p. 8-pg., 2020-01-05. (15/22145-6)

CAVALCANTI, DENISE P.; FANO, VIRGINIA; MELLADO, CECILIA; LACARRUBBA-FLORES, MARIA DORA J.; SILVEIRA, CYNTHIA; SILVEIRA, KARINA C.; DEL PINO, MARIANA; MORESCO, ANGELICA; CAINO, SILVIA; RAMOS MEJIA, ROSARIO; et al. Skeletal dysplasias in Latin America. AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS, v. 184, n. 4, p. 10-pg., 2020-11-21. (15/22145-6)

CAVALCANTI, DENISE P.; FANO, VIRGINIA; MELLADO, CECILIA; LACARRUBBA-FLORES, MARIA DORA J.; SILVEIRA, CYNTHIA; SILVEIRA, KARINA C.; DEL PINO, MARIANA; MORESCO, ANGELICA; CAINO, SILVIA; RAMOS MEJIA, ROSARIO; et al. Skeletal dysplasias in Latin America. AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS, v. 184, n. 4, SI, NOV 2020. (15/22145-6)

MEDINA, CRISTINA T. N.; SANDOVAL, RENATA; OLIVEIRA, GABRIELA; SILVEIRA, KARINA DA COSTA; CAVALCANTI, DENISE P.; POGUE, ROBERT. Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v. 182, n. 4, JAN 2020. (15/22145-6)

GOMES, MARIA E. S.; KANAZAWA, THATIANE Y.; RIBA, FERNANDA R.; PEREIRA, NATALYA G.; ZUMA, MARIA C. C.; RABELO, NATANA C.; SANSEVERINO, MARIA T.; HOROVITZ, DAFNE D. G.; LLERENA, JR., JUAN C.; CAVALCANTI, DENISE P.; et al. Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases in a Cohort of Brazilian Patients with Skeletal Dysplasia. MOLECULAR SYNDROMOLOGY, v. 9, n. 2, p. 92-99, 2018. (15/22145-6)

SILVEIRA, KARINA C.; MORENO, CAROLINA A.; CAVALCANTI, DENISE P.. Beemer-Langer syndrome is a ciliopathy due to biallelic mutations in IFT122. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v. 173, n. 5, p. 1186-1189, MAY 2017. (15/22145-6)

GOMES, MARIA E.; CALATRAVA PATERNOSTRO, LUIZA; MOURA, VALERIA R.; ANTUNES, DEBORAH; CAFFARENA, ERNESTO R.; HOROVITZ, DAFNE; SANSEVERINO, MARIA T.; FERRAZ LEAL, GABRIELA; FELIX, TEMIS M.; PONTES CAVALCANTI, DENISE; et al. Identification of Novel and Recurrent RMRP Variants in a Series of Brazilian Patients with Cartilage-Hair Hypoplasia: McKusick Syndrome. MOLECULAR SYNDROMOLOGY, v. 10, n. 5, p. 255-263, NOV 2019. (15/22145-6)

MOOSA, SHAHIDA; YAMAMOTO, GUILHERME L.; GARBES, LUTZ; KEUPP, KATHARINA; BELEZA-MEIRELES, ANA; MORENO, CAROLINA ARAUJO; VALADARES, EUGENIA RIBEIRO; DE SOUSA, SERGIO B.; MAIA, SOFIA; SARAIVA, JORGE; et al. Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta. American Journal of Human Genetics, v. 105, n. 4, p. 836-843, OCT 3 2019. (13/08028-1, 15/22145-6)

SILVEIRA, CYNTHIA; SILVEIRA, KARINA DA COSTA; LACARRUBBA-FLORES, MARIA D.; SAKATA, MAURICIO T.; CARBOGNANI, SILVIA N.; LLERENA JR, JUAN; MORENO, CAROLINA A.; CAVALCANTI, DENISE P.. SLC26A2/DTDST Spectrum: A Cohort of 12 Patients Associated with a Comprehensive Review of the Genotype-Phenotype Correlation. MOLECULAR SYNDROMOLOGY, v. N/A, p. 11-pg., 2022-06-15. (15/22145-6)

SILVEIRA, K. C.; MORENO, C. A.; SANSEVERINO, M.; RIBEIRO, E. M.; MELLADO, C.; BUCK, C. O. B.; BERNARDI, P.; GONCALVES, N.; OLIVEIRA, G. M.; LLERENA, J., JR.; et al. High success in the etiology determination of skeletal dysplasias from a custom NGS panel and identification of a gene related to Beemer-Langer syndrome. European Journal of Human Genetics, v. 26, p. 1-pg., 2018-10-01. (15/22145-6)

MEDINA, CRISTINA T. N.; SANDOVAL, RENATA; OLIVEIRA, GABRIELA; SILVEIRA, KARINA; CAVALCANTI, DENISE P.; POGUE, ROBERT. Pathogenic variants in the TRIP11 gene cause a skeletal dysplasia spectrum from odontochondrodysplasia to achondrogenesis 1A. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v. 182, n. 4, p. 681-688, APR 2020. (15/22145-6)

CHANG, HAE RYUNG; CHO, SUNG YOON; LEE, JAE HOON; LEE, EUNKYUNG; SEO, JIEUN; LEE, HYE RAN; CAVALCANTI, DENISE P.; MAKITIE, OUTI; VALTA, HELENA; GIRISHA, KATTA M.; et al. Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia. American Journal of Human Genetics, v. 104, n. 3, p. 439-453, MAR 7 2019. (15/22145-6)

JAZMIN LACARRUBBA-FLORES, MARIA DORA; CARVALHO, DANIEL ROCHA; RIBEIRO, ERLANE MARQUES; MORENO, CAROLINA ARAUJO; ESPOSITO, ANA CAROLINA; LIMA MARSON, FERNANDO AUGUSTO; LOUREIRO, THEREZA; CAVALCANTI, DENISE PONTES. Femoral-facial syndrome: A review of the literature and 14 additional patients including a monozygotic discordant twin pair. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, v. 176, n. 9, p. 1917-1928, SEP 2018. (15/22145-6)

SILVEIRA, KARINA C.; KANAZAWA, THATIANE Y.; SILVEIRA, CYNTHIA; LACARRUBBA-FLORES, MARIA D. J.; CARVALHO, BENILTON S.; CAVALCANTI, DENISE P.. Molecular diagnosis in a cohort of 114 patients with rare skeletal dysplasias. AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS, v. 187, n. 3, SI, SEP 2021. (15/22145-6)