Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases in a Cohort of Brazilian Patients with Skeletal Dysplasia

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 ge...

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Bibliographic Details
Published in:	Molecular syndromology Vol. 9; no. 2; pp. 92 - 99
Main Authors:	Gomes, Maria E.S., Kanazawa, Thatiane Y., Riba, Fernanda R., Pereira, Natálya G., Zuma, Maria C.C., Rabelo, Natana C., Sanseverino, Maria T., Horovitz, Dafne D.G., Llerena Jr, Juan C., Cavalcanti, Denise P., Gonzalez, Sayonara
Format:	Journal Article
Language:	English
Published:	Basel, Switzerland S. Karger AG 01-02-2018
Subjects:	Original Original Article Hypochondroplasia Achondroplasia High-resolution melting FGFR3 Thanatophoric dysplasia Double heterozygosity
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 by M. Schmid M.E.S.G., T.Y.K., D.P.C., and S.G. contributed equally to this work.
ISSN:	1661-8769 1661-8777
DOI:	10.1159/000486697