Spectrum of Genetic Mutations Among Iranian Patients with Gangliosidosis.

Abstract

Gangliosidosis is a hereditary metabolic disorder inherited in an autosomal recessive manner. This disorder is marked by the accumulation of gangliosides in the central nervous system, leading to considerable and progressive neurological deficits. In the current study, we described the clinical findings and genetic variations observed in 12 patients manifesting symptoms of gangliosidosis disorders. The results of molecular investigations revealed the presence of different variants in the HEXA (three cases), HEXB (four cases) and GLB1 genes (five cases) in the patients. Notably, the c.833C > T (p.A278V) variant in the HEXB was detected in two unrelated cases. Four novel variants were also detected, including two likely pathogenic variants in the HEXB gene, namely c.1083-2del and c.1616_1622dup (p.Ile541Metfs*14). A single case had three variants in the GLB1 gene, including two novel variants (c.545C > T and c.631G > C); and a previously reported pathogenic variant (c.601C > T). The current study broadens the spectrum of genetic variations in Iranian patients with different types of gangliosidosis. This information is also important for the process of genetic counseling in the affected families.