Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel based sequencing for differential diagnosis of gangliosidosis

Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

“…This deletion was perfectly segregating with the phenotype and the genomic region only contains two rare CNVs in human populations in the gnomAD structure variation database ( https://gnomad.broadinstitute.org/region/5–73980065-73992881?dataset=gnomad_sv_r2_1 ). HEXB encodes a subunit of the lysosomal enzyme beta-hexosaminidase, and mutations in HEXB has been associated with neurodegenerative Sandhoff disease 58 . The second CNV is a heterozygous deletion in FAM9 (g.chr20:5281253–5289644).…”

Highlights on Genomics Applications for Lysosomal Storage Diseases

“…This is particularly useful when applied to specific diagnostic contexts, including carrier screening studies in high-risk populations (e.g., the Ashkenazi Jewish population) [ 60 , 61 ], prenatal diagnosis [ 62 ], unsolved cases where traditional molecular diagnostic approaches have failed [ 63 ], unclear or suspected LSD cases [ 64 , 65 ], as well as in defining genotype–phenotype correlations [ 66 ] or to find out genetic disease modifiers [ 67 ]. More interesting is the use of NGS to differentiate genetically heterogeneous diseases with overlapping clinical phenotypes, such as Pompe disease, limb-girdle muscular dystrophies [ 68 , 69 ], and Gangliosidosis [ 70 ], or to investigate mosaic conditions [ 71 , 72 ]. Many companies developed commercial panels and offer direct-to-consumer sequencing services for suspected LSD cases, utilizing custom panels that target few or many genes (causative genes, lysosomal pathway-related genes, or peroxisome disorder-related genes) and are based on arbitrary research ( Supplementary Table S2 ).…”