De Novo Large Deletion Leading to Fragile X Syndrome

Poonnada Jiraanont; Esther Manor; Nazi Tabatadze; Marwa Zafarullah; Guadalupe Mendoza; Gia Melikishvili; Flora Tassone

doi:10.3389/fgene.2022.884424

De Novo Large Deletion Leading to Fragile X Syndrome

Front Genet. 2022 May 11:13:884424. doi: 10.3389/fgene.2022.884424. eCollection 2022.

Authors

Poonnada Jiraanont¹, Esther Manor^{2

3}, Nazi Tabatadze⁴, Marwa Zafarullah⁵, Guadalupe Mendoza⁵, Gia Melikishvili⁴, Flora Tassone^{5

6}

Affiliations

¹ Faculty of Medicine, King Mongkut's Institute of Technology Ladkrabang, Bangkok, Thailand.
² Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
³ Genetics Institute, Soroka Medical Center, Beersheba, Israel.
⁴ Department of Pediatrics, MediClub Georgia Medical Center, Tbilisi, Georgia.
⁵ Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, CA, United States.
⁶ UC Davis MIND Institute, UC Davis Health, Sacramento, CA, United States.

Abstract

Fragile X syndrome (FXS) is the most frequent cause of X-linked inherited intellectual disabilities (ID) and the most frequent monogenic form of autism spectrum disorders. It is caused by an expansion of a CGG trinucleotide repeat located in the 5'UTR of the FMR1 gene, resulting in the absence of the fragile X mental retardation protein, FMRP. Other mechanisms such as deletions or point mutations of the FMR1 gene have been described and account for approximately 1% of individuals with FXS. Here, we report a 7-year-old boy with FXS with a de novo deletion of approximately 1.1 Mb encompassing several genes, including the FMR1 and the ASFMR1 genes, and several miRNAs, whose lack of function could result in the observed proband phenotypes. In addition, we also demonstrate that FMR4 completely overlaps with ASFMR1, and there are no sequencing differences between both transcripts (i.e., ASFMR1/FMR4 throughout the article).

Keywords: ASFMR1/FMR4 gene; FMR1 gene; fragile X syndrome; large deletion; miRNA.