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  • Updated 09.24.2021
  • Released 07.17.2000
  • Expires For CME 09.24.2024

Molecular diagnosis of neurologic disorders



Molecular diagnosis is the clinical application of molecular technologies to elucidate, diagnose, and monitor human diseases. This article introduces basic technologies and new developments for application in clinical diagnostics. These technologies are important for precise and rapid diagnosis of diseases of the nervous system such as infections, brain tumors, genetic disorders, and neurodegenerative diseases. Introduction of nanotechnology in diagnostics has further refined these procedures.

Key points

• Molecular diagnosis is the clinical application of molecular technologies to refine diagnosis.

• Many new biotechnologies have been incorporated in molecular diagnostics including biochips and nanobiotechnology.

• Next-generation sequencing is having an increasing impact on molecular diagnostics as sequencing of the human genome becomes more affordable.

• Molecular diagnostics has important applications in neurology including genetic disorders, infections, and cancer of the nervous system.

• Besides diagnosis of disease, molecular diagnostic technologies are also useful for drug discovery, monitoring of therapy by using biomarkers, and the development of personalized neurology.

Historical note and terminology

Molecular diagnosis can be defined as the clinical application of molecular technologies to elucidate, diagnose, and monitor human diseases. Basic technologies have been described in detail elsewhere (19). Molecular technologies incorporate the use of nucleic acids (DNA and RNA) as well as recombinant antibodies. Proteomic technologies are also applied to molecular diagnosis, justifying the term "proteodiagnostics." More than 500 molecular diagnostic systems have been developed to date. This article describes the basic principles of these technologies and their application to the diagnosis of neurologic disorders. The College of American Pathologists has used the term molecular pathology for molecular diagnostics, and as an extension of this, the application for neurologic disorders can be considered as molecular neuropathology." Imaging technologies have been refined to the molecular level and the term "molecular brain imaging" is suggested.

Landmarks in the historical development of molecular diagnostics appear in Table 1. DNA was shown to carry genetic code in pneumococci (01) even before the discovery of the double-stranded structure of the DNA (42). DNA probes (segments of DNA labeled with radioactive markers) were used for diagnostic purposes in the 1980s, but the most important landmark in molecular diagnostics was the discovery of polymerase chain reaction (PCR) in 1985 (30). In the pre-PCR era, molecular biologists needed cumbersome and slow laboratory methods to study a few copies of a DNA sequence of interest in a clinical sample. Polymerase chain reaction, by providing unlimited copies of DNA, facilitated the applications in clinical diagnostics. Although several other technologies for amplification and detection of nucleic acids have been developed since then, PCR, with its modifications, remains the mainstay of current molecular diagnosis.

Availability of the human genome sequence will provide opportunities for the development of molecular diagnostics. This will lead to the development of novel diagnostics as well as therapeutics for neurologic disorders and facilitate the development of personalized neurology.

Table 1. Historical Development of Molecular Diagnostics


Discovery and development


DNA shown to carry genetic code in pneumococci (01)


Identification of the double-stranded structure of DNA (42)


Discovery of the enzyme DNA polymerase (25)


Discovery of in situ hybridization for gene location by labeled RNA probes (09)


Discovery of restriction enzymes that cut DNA at the site of specific sequences


Discovery of reverse transcriptase and copying of RNA into DNA (02)


First recombinant DNA molecule is produced with use of ligase. The genomic age begins (13).


Southern blot test (38)


Monoclonal antibody technology (24)


Invention of the technology for DNA sequencing (34)


Creation of the first recombinant DNA molecule


Gene mapping by in situ hybridization becomes a standard method


DNA probes: segments of DNA labeled with radioactive markers


Demonstration of Huntington disease gene (11)


Discovery of polymerase chain reaction at Cetus Corporation (30)

1987 and 1988

Discovery of dystrophin, the protein product of the human Duchenne muscular dystrophy locus, and its characterization in muscle biopsies by immunoblotting (12)


Development of fluorescent in situ hybridization technique (33)


Start of Human Genome Project, National Institutes of Health, USA


Ligase chain reaction (03)


Wedding of molecular biology and cytogenetics to create molecular cytogenetics (27)


Peptide nucleic acid, a mimic of DNA, is invented. Peptide nucleic acid arrays are useful for detection of DNA and RNA (32).


Branched DNA technology used to quantify HIV levels


Invention of locked nucleic acid, a DNA analogue with a high affinity for complementary DNA or RNA and the ability to discriminate between correct and incorrect target sequences (26)


Antisense oligonucleotides labeled to detect RNA and tracked in their sojourn through the body by PET (39)


Sequencing of human genome is completed. The postgenomic era begins.


Application of proteomic technologies in diagnosis: proteodiagnostics


Application of nanotechnologies in diagnosis: nanodiagnostics

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