| Author | Gomes, Maria E. S. | |
| Author | Kanazawa, Thatiane Y. | |
| Author | Riba, Fernanda R. | |
| Author | Pereira, Natálya Gonçalves | |
| Author | Zuma, Maria C. C. | |
| Author | Rabelo, Natana C. | |
| Author | Sanseverino, Maria T. | |
| Author | Horovitz, Dafne Dain Gandelman | |
| Author | Llerena Junior, Juan Clinton | |
| Author | Cavalcanti, Denise P. | |
| Author | Gonzalez, Sayonara | |
| Access date | 2019-11-26T16:28:16Z | |
| Available date | 2019-11-26T16:28:16Z | |
| Document date | 2018 | |
| Citation | GOMES, Maria E. S. 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, p. 1-8, 2018. | pt_BR |
| ISSN | 1661-8769 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/37397 | |
| Language | en | |
| Rights | restricted access | |
| Title | Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases in a Cohort of Brazilian Patients with Skeletal Dysplasia | pt_BR |
| Type | Article | |
| DOI | 10.1159/000486697 | pt_BR |
| Abstract | Mutations in the fibroblast growth factor receptor 3 gene (FGFR3) cause achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types I and II (TDI/TDII). In this study, we performed a genetic study of 123 Brazilian patients with these phenotypes. Mutation hotspots of the FGFR3 gene were PCR amplified and sequenced. All cases had recurrent mutations related to ACH, HCH, TDI or TDII, except for 2 patients. One of them had a classical TDI phenotype but a typical ACH mutation (c.1138G>A) in combination with a novel c.1130T>C mutation predicted as being pathogenic. The presence of the second c.1130T>C mutation likely explained the more severe phenotype. Another atypical patient presented with a compound phenotype that resulted from a combination of ACH and X-linked spondyloepiphyseal dysplasia tarda (OMIM 313400). Next-generation sequencing of this patient's DNA showed double heterozygosity for a typical de novo ACH c.1138G>A mutation and a maternally inherited TRAPPC2 c.6del mutation. All mutations were confirmed by Sanger sequencing. A pilot study using high-resolution melting (HRM) technique was also performed to confirm several mutations identified through sequencing. We concluded that for recurrent FGFR3 mutations, HRM can be used as a faster, reliable, and less expensive genotyping test than Sanger sequencing. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Medicina Genômica. Departamento de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Estadual de Campinas. Departamento de Genética Médica. Grupo de Displasias Esqueléticas. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Medicina Genômica. Departamento de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Centro de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Medicina Genômica. Departamento de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Medicina Genômica. Departamento de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio Grande do Sul. Porto Alegre, RS, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Centro de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Centro de Genética Médica. Rio de Janeiro, RJ, Brasil / Faculdade de Medicina de Petrópolis. Faculdade Arthur Sá Earp Neto. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Genética Médica Populacional. Porto Alegre, RS, Brasil. | pt_BR |
| Affilliation | Universidade Estadual de Campinas. Departamento de Genética Médica. Grupo de Displasias Esqueléticas. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Laboratório de Medicina Genômica. Departamento de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Achondroplasia | pt_BR |
| Subject | Double heterozygosity | pt_BR |
| Subject | FGFR3 | pt_BR |
| Subject | High-resolution melting | pt_BR |
| Subject | Hypochondroplasia | pt_BR |
| Subject | Thanatophoric dysplasia | pt_BR |
| Embargo date | 2200-01-01 | |
