WES and WGS through NGS for neurological disease
Investigation of a possible neurogenetic disorder begins with assessment of the patient’s phenotype. Depending on the findings, the physician refers the patient for the appropriate genetic analysis.
Whole-exome sequencing (WES, 100X) and whole-genome sequencing (WGS, 30X) use next-generation sequencing and can detect small deletions, duplications and single-nucleotide variants. Disorders caused by large rearrangements, chromosomal abnormalities or repeat expansions require other molecular analyses.
NGS may be used for disease-targeted multigene panels, all coding exons (WES), or the whole genome (WGS). WES examines coding regions where many disease-causing variants occur and may identify known or novel variants, secondary findings, carrier status and pharmacogenetic variants.
Mitochondrial DNA
Mitochondrial DNA contains 37 genes encoding 13 proteins, 22 transfer RNAs and 2 ribosomal RNAs. Mitochondria support energy production and participate in calcium regulation, apoptosis and metabolism. Mitochondrial-DNA disorders may affect the eye, hearing, hormones, heart, gastrointestinal tract, nervous system, muscles, liver and kidneys.
Depending on phenotype and family history, the specialist may request complete mitochondrial-genome analysis by NGS or targeted Sanger sequencing.
Selected mitochondrial syndromes
MELAS (MT-TL1, MT-ND3, MT-ND5, MT-CYTB); CPEO (MT-TV, MT-TL2); Kearns–Sayre (large mitochondrial-DNA deletion); MIDD (MT-TL1, MT-ND1); MERRF (MT-TK, MT-ND5); LHON (MT-ND1, MT-CO3, MT-ND6, MT-ND4); Leigh syndrome and NARP (MT-ATP6, MT-ND6, MT-ND4); Pearson syndrome (large mitochondrial-DNA deletion).