Background: Faciogenital Dysplasia Gene (FGD1) mutations are seen to be underlined causes of the broad spectrum of Aarskog-Scott syndrome (ASS) as well as Non-Syndromic X-linked intellectual disability. The protein FGD1 is an important regulator of events that control extracellular matrix remodeling, bone development, cell migration and also involved in the regulation of few secretory proteins. The reported mutations suggest that non-coding variants are equally important for disease progression. The current study tests manifestations of intronic variant SNP rs2239809 of FGD1 in intellectually disabled children.
Methods: The selection of associated intronic variants of FGD1 gene was performed using GWAS (Genome Wide Association Study) central database and GWAS 3D web server. PCRRFLP was performed for screening of selected intronic variants. Sanger sequencing was used to validate single nucleotide change in FGD1 gene. Clinical features were studied and compared; partial pedigree was recorded for affected patients. Results: In this study, significant alteration was found in two affected children from different family harboring intronic variant NM_004463.2: c.659+27T>C (rs2239809) at intron 3 of FGD1 gene. Surprisingly, female and male showed different phenotypic appearance for the same variation.
Conclusion: The present study provides significant insight that intronic variant rs2239809 affects FGD1 gene functions and on the basis of computational study this variant active for transcription regulation process. The study need to translate the computational genetic signals into biological mechanism of Transcription Factor Binding Site (TFBS) affinity of this intronic variant.