Novel Hemizygous Missense Variation in AFF2 Gene Underlies Fragile XE Syndrome

Background: Fragile XE (FRAXE) is an X-linked recessive condition of intellectual disability affecting 1 in 50,000 new born male. FRAXE is characterized by mild ID, cognitive impairment, speech delay and some cases patients display Autism Spectrum disorder (ASD) like phenotypes. . Method: In this study, we investigated a family with two male siblings with neurodevelopmental delay Whole exome sequencing analysis (WES) was employed to identify the pathogenic variant. Co-segregation analysis was performed through Sanger sequencing in affected and normal family members. Results: Two affected Proband of family were diagnosed with intellectual disability. A novel hemizygous variant, c.3348G>T; p.Asp1150Tyr, in AFF2 gene was identified as the pathogenic cause in affected individuals. It is first novel variant report in AFF2 gene within Pakistani population. Conclusion : In this study, novel hemizygous variant, c.3348G>T; p.Asp1150Tyr, in AFF2 gene was identified. The findings broaden the clinical and genetic spectrum of rare X-linked recessive disorders causing ID.