Many of the neurological disorders discussed in this book have a genetic etiology that can be diagnosed and/or confirmed by chromosomal or molecular testing. Due to advances in genetic technology, the range of testing options has increased dramatically in the last few years. Deciding which test to perform and how to interpret the results can be daunting. Accordingly, in this chapter we review the different types of clinically available genetic tests. These can be employed for general screening or for confirmation of a clinically diagnosed condition. The general portfolio of such testing is illustrated in Table 21-1, and this chapter will review these types of tests.
Table 21–1. Common Types of Genetic and/or Metabolic Tests That May Be Obtained During a Neurological Evaluation |Favorite Table|Download (.pdf)
Table 21–1. Common Types of Genetic and/or Metabolic Tests That May Be Obtained During a Neurological Evaluation
- Routine G-banded analysis
- Single FISH probe study (eg, for Angelman syndrome)
- Multiple probe FISH study (eg, subtelomeres)
- Array-based comparative genomic hybridization (CGH)
|Molecular Mutation-Based Tests|
- Single mutation study
- Multiple mutation screens (eg, Charot-Marie-Tooth multigene panel)
- Complete gene sequencing and/or gene deletion study (eg, Neurofibromatosis, type)
- Trinucleotide repeat analysis (eg, for Fragile X)
- DNA methylation study (eg, to rule out Prader-Willi syndrome)
- Single nucleotide polymorphism (SNP) analysis (eg, to rule out uniparental disomy)
- Mitochondrial DNA (mtDNA) sequence analysis
- Southern blot study for mtDNA deletions and duplications
- Electron transport function (ETF) assays
- Urine organic acids
- Plasma amino acids
- Plasma acylcarnitine profile
- Enzyme Assay (eg, Lysosomal Enzymes)
A routine chromosome study (karyotype) involves evaluating the chromosomes during the metaphase period of cell mitosis, and the test is usually performed on blood cells. Lymphocytes are grown in culture and stained with a dye such as Giemsa to obtain a distinct pattern of light and dark bands. This banding pattern is unique to each of the 46 chromosomes, and helps to identify them on microscopic examination (Figure 21-1). A routine chromosome study can identify extra or missing chromosomes (eg, Down [47, XY+21] and Klinefelter [47, XXY] syndromes) as well as detect large inversions, translocations, deletions, duplications, and extra fragments (eg, marker chromosomes). The visual resolution of this study, however, is only at the 10 to 20 million base pair level (Table 21-2). Higher-resolution tests are available (as discussed below in Array-Based Comparative Genomic Hybridization) that detect much smaller changes in the chromosome.
Table 21–2. Sensitivity of Different Genetic Tests to Detect DNA Changes. |Favorite Table|Download (.pdf)
Table 21–2. Sensitivity of Different Genetic Tests to Detect DNA Changes.
|Type of test||Detection size*|
|Routine chromosome study||10-20 million|
|Individual FISH||3-5 million|
|Subtelomere FISH panel||3-5 million per probe|
|Low resolution (~1200 probes)||400,000-1.5 million|
|High resolution (~10-90,000 probes)||(30,000-300,0000)|
|Gene deletion, gene duplication testing||30,000-800,0000 depending on ...|
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