Clinical and Molecular Characteristics of Two Chinese Children with Infantile Sandhoff Disease and Review of the Literature.

Infantile Sandhoff disease is an autosomal recessive inherited disease primarily characterized by cherry red spots in the retina, muscle weakness, seizure, truncal hypotonia, hyperacusis, developmental delay and regression. The pathogenic genetic defects of the HEXB gene, which encodes the β subunit of the hexosaminidase A (ɑβ) and hexosaminidase B (ββ) enzymes, cause deficiency of both the Hex A and Hex B enzymes, resulting in the deposition of GM2 ganglion glycerides in the lysosomes of the central nervous system and somatic cells. The aim of this study was to discover disease-causing variants of the HEXB gene in two Chinese families through the use of exome sequencing. By characterizing three novel variants by molecular genetics, bioinformatics analysis, and three-dimensional structure modeling, we showed that all these novel variants influenced the protein structure. The results broaden the variant spectrum of HEXB in different ethnic groups. Furthermore, not all patients diagnosed with infantile Sandhoff disease had characteristic cranial imaging findings, which can only be used as supplementary information for diagnosis. The results of this study may contribute to clinical management, genetic counseling, and gene-targeted treatments for Sandhoff disease.