A Novel Hemizygous Variant in the AFF2 Gene Causing Fragile XE (FRAXE) Syndrome: First Report from Pakistan

Abstract

Background: Fragile XE (FRAXE) is an X-linked recessive condition that affects 1 in 50,000 of new born males with intellectual disability (ID). It is characterized by mild Intellectual disability (ID), speech delay cognitive impairment, and in some cases with phenotypes of Autism Spectrum disorder (ASD).

Methodology: In this study, a family was investigated with two male siblings having neuro developmental delay. Whole exome sequencing analysis (WES) was carried out to identify the pathogenic variant. Sanger sequencing was performed in normal and affected family members and co-segregation analysis was done.

Results: Two probands were affected in a family diagnosed with intellectual disability. A novel hemizygous variant (c.3348G>T, p.Asp1150Tyr) in AFF2 gene was identified as the causal variant cause in affected individuals. This variant was novel from Pakistani population.

Conclusion: In this study, a novel hemizygous variant (c.3348G>T, p.Asp1150Tyr) identified in AFF2. These findings paved the way for further studies on genetic and clinical spectrum of rare X-linked recessive disease involved in ID.