Identification of the FGFR3<sup>G380R</sup> Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling Approach
Mutations in the gene for fibroblast growth factor receptor 3 (FGFR3) are implicated in achondroplasia, an autosomal-dominant form of short-limbed dwarfism. The present study involves a combination of clinical exome sequencing, targeted resequencing and protein modeling methods to decipher the patho...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-12-01
|
| Series: | Proceedings |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2504-3900/2/25/1551 |
| id |
doaj-567a0c91281445dc96f609013426a51b |
|---|---|
| record_format |
Article |
| spelling |
doaj-567a0c91281445dc96f609013426a51b2020-11-24T20:49:10ZengMDPI AGProceedings2504-39002018-12-01225155110.3390/proceedings2251551proceedings2251551Identification of the FGFR3<sup>G380R</sup> Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling ApproachKerem Teralı0Department of Medical Biochemistry, Faculty of Medicine, Near East University, 99138 Nicosia, Mersin 10, TurkeyMutations in the gene for fibroblast growth factor receptor 3 (FGFR3) are implicated in achondroplasia, an autosomal-dominant form of short-limbed dwarfism. The present study involves a combination of clinical exome sequencing, targeted resequencing and protein modeling methods to decipher the pathobiology of achondroplasia with psychomotor delay in a two-year-old child. Accordingly, the resulting genetic information establishes the frequent <i>FGFR3</i> c.1138G > A (p.G380R) mutation as the single hit causing pediatric achondroplasia with psychomotor delay, while the predicted model stresses the importance of a phenylalanyl residue (F384) in enhancing the dimerization potential of the receptor’s transmembrane domain via a cation‒π interaction with the newly introduced arginyl residue. Overall, the likely involvement of FGFR3<sup>G380R</sup> in psychomotor delay calls for comprehensive clinical assessment in achondroplastic children, although the precise mechanism by which the mutant receptor results in the development of neurological manifestations awaits further investigation.https://www.mdpi.com/2504-3900/2/25/1551achondroplasiapsychomotor delayfibroblast growth factor receptor 3clinical exome sequencingbiomolecular modeling |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Kerem Teralı |
| spellingShingle |
Kerem Teralı Identification of the FGFR3<sup>G380R</sup> Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling Approach Proceedings achondroplasia psychomotor delay fibroblast growth factor receptor 3 clinical exome sequencing biomolecular modeling |
| author_facet |
Kerem Teralı |
| author_sort |
Kerem Teralı |
| title |
Identification of the FGFR3<sup>G380R</sup> Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling Approach |
| title_short |
Identification of the FGFR3<sup>G380R</sup> Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling Approach |
| title_full |
Identification of the FGFR3<sup>G380R</sup> Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling Approach |
| title_fullStr |
Identification of the FGFR3<sup>G380R</sup> Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling Approach |
| title_full_unstemmed |
Identification of the FGFR3<sup>G380R</sup> Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling Approach |
| title_sort |
identification of the fgfr3<sup>g380r</sup> mutant as a likely cause of psychomotor delay in an achondroplastic child: a combined clinical exome sequencing and biomolecular modeling approach |
| publisher |
MDPI AG |
| series |
Proceedings |
| issn |
2504-3900 |
| publishDate |
2018-12-01 |
| description |
Mutations in the gene for fibroblast growth factor receptor 3 (FGFR3) are implicated in achondroplasia, an autosomal-dominant form of short-limbed dwarfism. The present study involves a combination of clinical exome sequencing, targeted resequencing and protein modeling methods to decipher the pathobiology of achondroplasia with psychomotor delay in a two-year-old child. Accordingly, the resulting genetic information establishes the frequent <i>FGFR3</i> c.1138G > A (p.G380R) mutation as the single hit causing pediatric achondroplasia with psychomotor delay, while the predicted model stresses the importance of a phenylalanyl residue (F384) in enhancing the dimerization potential of the receptor’s transmembrane domain via a cation‒π interaction with the newly introduced arginyl residue. Overall, the likely involvement of FGFR3<sup>G380R</sup> in psychomotor delay calls for comprehensive clinical assessment in achondroplastic children, although the precise mechanism by which the mutant receptor results in the development of neurological manifestations awaits further investigation. |
| topic |
achondroplasia psychomotor delay fibroblast growth factor receptor 3 clinical exome sequencing biomolecular modeling |
| url |
https://www.mdpi.com/2504-3900/2/25/1551 |
| work_keys_str_mv |
AT keremteralı identificationofthefgfr3supg380rsupmutantasalikelycauseofpsychomotordelayinanachondroplasticchildacombinedclinicalexomesequencingandbiomolecularmodelingapproach |
| _version_ |
1716806593270513664 |