Screening for Familial Hypercholesterolemia in Tunisia using Whole Exome Sequencing: Importance in diagnosis and...

To determine pathogenic variants linked to Familial Hypercholesterolemia (FH) among a southern Tunisian family using Whole Exome Sequencing (WES).

Genomic DNA was extracted from whole blood among the index case as well as other affected and unaffected family members. Then, WES was performed only in the proband. The pathogenicity of genetic variation was assessed in a set of 13 genes reported as associated with FH using combined filtering and bioinformatics prediction tools. Finally, sanger sequencing was done to verify the probands' likely pathogenic predicted mutations and to check for familial segregation among all family subjects.

Our results showed the presence of a pathogenic splice site mutation (c.1186+1G>A) in the LDLR gene among the proband and other affected family members. The following up of the family, revealed the effectiveness of the combination of rosuvastatin and ezetimibe with healthy diet to meet the LDL-c treatment goal with approximately 50% of decrease for the proband.

This study is the first of its kind using WES for FH screening and diagnosis in Tunisia. Here, we point up the importance of molecular analysis for a better health care management of FH patients and their families.