The role of molecular biology laboratory in the definition of genetic alterations: a case of Gaucher disease

We report about a 51-year-old patient with a severe clinical history and a diagnosis of Gaucher disease at the age of 4 years, based on the beta glucosidase enzyme activity test. The patient underwent molecular investigation using a Next-Generation Sequencing (NGS) method to define his genotype. Genetic analysis showed the presence of two variants in the GBA1 gene: c.626G>C and c.1225-14_1225-11delinsAGT. The mRNA analysis of the possible splicing variant, c.1225-14_1225-11 delinsAGT classified as variant of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) criteria, revealed the formation of a cryptic splicing site. The mRNA analysis enabled the definitive reclassification of the variant as likely pathogenic (LP) and led to correctly defining the patient’s genotype and to improve genetic counseling in the families. Our study highlights the need for integration between the diagnostic laboratory and the molecular biology laboratory.