Identification of the FGFR3G380R Mutant As a Likely Cause of Psychomotor Delay in an Achondroplastic Child: A Combined Clinical Exome Sequencing and Biomolecular Modeling Approach

Proceedings

Teralı, Kerem¹  Gülsün Temel, Şehime²  Eren, Erdal³ 

[1] Department of Medical Biochemistry, Faculty of Medicine, Near East University, 99138 Nicosia, Mersin 10, Turkey;Department of Medical Genetics, Faculty of Medicine, Uludağ University,16059 Bursa, Turkey;Department of Pediatric Endocrinology, Faculty of Medicine, Uludağ University, 16059 Bursa, Turkey

关键词: achondroplasia;    psychomotor delay;    fibroblast growth factor receptor 3;    clinical exome sequencing;    biomolecular modeling;   

DOI  :  10.3390/proceedings2251551

学科分类：社会科学、人文和艺术（综合）

来源: mdpi

【 摘 要 】

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 FGFR3 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 FGFR3G380R 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.

【 授权许可】

CC BY