Aarskog-Scott syndrome results from various changes in the DNA sequence of the FGD1 gene. These variants cause a loss of the function of the normal product of the gene, the protein FGD1. They either result in the absence of production of the protein or produce a non-functional protein due to a change in its structure. The DNA changes may be located in different parts of the gene. In most cases, the gene defect is present in the family and transmitted by a carrier mother, but in around 10% of cases it arises de novo in a child by the sudden occurrence of a mutation in the DNA sequence.
Causal variants may be detected by different lab methods. Analysis of the FGD1 gene is possible when the diagnosis is clinically obvious or strongly suspected. If no precise diagnosis is suggested, analysis of a panel of genes dedicated to congenital malformations and/or neurodevelopment problems is usually performed. However, nowadays, pangenomic analyses - i.e. analysis of all genes of the genome or analysis of the whole genome – are becoming more and more usual. In case no pathogenic variant is detected, although the diagnosis is obvious or highly probable, Aarskog-Scott syndrome is not excluded, and the molecular lab must be aware of the possibility of particular gene changes which require the use an appropriate method of detection.
FGD1