Fibroblast Growth Factor Receptor 2 (FGFR2), a New Gene Involved in the Genesis of Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a long-known complex neurodevelopmental disorder, and over the past decades, with the enhancement of the research genomic techniques, has been the object of intensive research activity, and many genes involved in the development and functioning of the central nervous system have been related to ASD genesis. Herein, we report a patient with severe ASD carrying a G > A de novo variant in the FGFR2 gene, determining a missense mutation. FGFR2 encodes for the ubiquitous fibroblast growth factor receptor (FGFR) type 2, a tyrosine kinase receptor implicated in several biological processes. The mutated version of this protein is known to be responsible for several variable overlapping syndromes. Even if there still is only sparse and anecdotal data, recent research highlighted a potential role of FGFR2 on neurodevelopment. Our findings provide new insights into the potential causative role of FGFR2 gene in complex neurodevelopmental disorders.

Keywords: Autism; FGFR2 gene; Human chromosome 10; Intellectual disability; Missense mutation; Sanger sequencing.

Fig. 1

Heterozygous variant identified in the present ASD patient. A genomic organization of the FGFR2 gene localized in the chromosomal band 10q26.13. Gene is transcribed from the telomere to the centromere side and consists of 18 exons. Exon 4 contains the detected C > T variation (G > A in the RefSeq NM_000141.5). B Nucleotide and aminoacidic sequences of the FGFR2 gene exon-4. The red asterisk indicates the nucleotide and the corresponding aminoacidic variant. The horizontal black line indicates the direction of transcription/translation. Data and images from the UCSC Genome Browser (http://genome.ucsc.edu, accessed on 15 June 2023). C Sanger sequencing electropherogram of the 21 nucleotides surrounding the C > T variant, showing the heterozygous missense mutation detected in the ASD patient, respect to his parents. A black box highlights the mutated nucleotide

Fig. 2

Expression level of the FGFR2 gene in human healthy tissues. The expression level was obtained in 54 human tissues from GTEx RNA-seq of 17,382 samples from 948 donors (V8, Aug 2019). TPM: Transcripts per Million. Data and image from the UCSC Genome Browser (http://genome.ucsc.edu, Accessed 05 May 2023)