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NEUROGENETICS LAB

NEUROGENETICS LABORATORY

CLINICAL SERVICE

The discovery of DNA as the molecule carrying genetic information and the deciphering of the genetic code had revolutionary consequences in the field of biological sciences. Molecular biology, offering an etiological molecular diagnosis to inherited diseases, is leading to a radical, albeit gradual, change to our concept of genetic disorders and their treatment. Molecular genetic analysis allows the identification of pathogenic variants within the genome, which lead to specific genetic diseases.  Thus, through the use of specific genetic tests, pathogenic variants that are often pathognomonic of a certain disease can be identified, allowing precise diagnosis of symptomatic individuals, but also tracing of asymptomatic carriers of pathogenic mutations. This leads to focused and comprehensive genetic counselling and effective prenatal genetic diagnosis.

In appropriately designed laboratory space and according to international guidelines, the Neurogenetics Unit, which comprises the Neurogenetics laboratory and the Neurogenetics outpatient Clinic, performs molecular diagnosis, carries out applied research, and also develops novel molecular diagnostic techniques.

The neurogenetics laboratory offers molecular diagnosis for the following hereditary disorders of the nervous system (neurogenetic diseases):

  • Hereditary motor and sensory neuropathies or Charcot-Marie Tooth disease (CMT)

-      CMT1A.  Methodology: molecular testing utilizing a technique known as MLPA (Multiplex Ligation-dependent Probe Amplification) and analysis on the ABI 3500 Genetic Analyzer. 

-      CMTX.  Methodology: DNA sequencing of exon 2 of GJB1 coding for connexin-32 using labeled dideoxynucleotide probes and analysis on the ABI 3500 Genetic Analyzer.

-      HNPP.  Methodology: molecular testing utilizing a technique known as MLPA (Multiplex Ligation-dependent Probe Amplification) and analysis on the ABI 3500 Genetic Analyzer. 

-      CMT4C. Methodology: Targeted identification of the mutation c.2860 C>T in gene SH3TC2 (CMT4C) using PCR and restriction fragment length polymorphisms (RFLP).

    • Friedreich’s ataxia (FRDA)

Methodology: Determination of repeat expansion in the 1st intron of the FXN gene coding for frataxin in chromosome 9q13, using long-PCR (long-range polymerase chain reaction), combined with TP-PCR (repeat-primed polymerase chain reaction using 3 primers), followed by fragment analysis on the ABI 3500 Genetic Analyzer. 

    • Spinocerebellar ataxias(SCA1, SCA2, SCA3, SCA6 and SCΑ7)

Methodology: Determination of CAG repeat expansion in the genes ATXN1, ATXN2, ATXN3, CACANA1A and ATXN7, using fluorescent PCR (polymerase chain reaction), followed by fragment analysis on the ABI 3500 Genetic Analyzer. 

    • Huntington’s disease (HD)

Methodology: Determination of CAG repeat expansion in exon 1 of HTT gene on chromosome 4p16.3 using fluorescent PCR (polymerase chain reaction), followed by fragment analysis on the ABI 3500 Genetic Analyzer. 

    • Myotonic dystrophy type 1 (DM1)

Methodology: Determination of non-coding CTG repeat expansion in the DMPK gene, using PCR, long-PCR (long-range polymerase chain reaction), combined with TP-PCR (repeat-primed polymerase chain reaction using 3 primers), followed by fragment analysis on the ABI 3500 Genetic Analyzer.

    • Spinal and bulbar muscular atrophy or Kennedy’s disease (SBMA,  KAS)

Methodology: Determination of CAG repeat expansion in exon 1 of AR (androgen receptor) gene on chromosome Xq12 using fluorescent PCR (polymerase chain reaction), followed by fragment analysis on the ABI 3500 Genetic Analyzer.

    • Parkinson’s disease

Methodology: Targeted identification of the mutation c.157 G>A (p.A53T) in the SNCA gene (PARK1) using PCR and restriction fragment length polymorphisms (RFLP).

    • Familial Amyloid Polyneuropathy (FAP)

Methodology: DNA sequencing   of the transthyretin, TTR  gene coding sequence, using labeled dideoxynucleotide probes and analysis on the ABI 3500 Genetic Analyzer.

 

It should be noted that the aforementioned molecular biological techniques offer a >99% diagnostic accuracy. Both the accuracy and the reproducibility of these techniques have been certified by the EMQN (European Molecular Genetics Quality Network).

ISO 15189:2022 accreditation  by ESYD (Hellenic Accreditation System)

 

PREREQUISITES

Who can be tested: molecular diagnosis for symptomatic individuals can be requested, where appropriate, by the treating physician or the patient him-/herself. 

Presymptomatic testing for individuals at high risk of inheriting a genetic disorder is only carried out following appropriate genetic counselling, given usually in two sessions separated by a two-month ‘cool-down’ period, in cases where it is deemed necessary (early manifest disease, prevention of future complications, pending pregnancy, carrier tracing) and safe (psychological sequelae). It should be noted that presymptomatic testing for non-adults is not recommended, with a few exceptions such as myotonic dystrophy or Friedreich’s ataxia, multisystem disorders in which genetic testing allows prevention of dysfunction in other systems.

Blood sample: For molecular genetic testing the laboratory requires 10cc of whole blood in a plastic EDTA tube (full blood count tube). This should be accompanied by a form with detailed clinical notes and comprehensive family tree.

Informed consent: Written informed consent is necessary for the performance of molecular genetic testing. Genetic results are strictly confidential and are given to the individual under investigation or the referring physician. For another person to receive genetic results, signed authorization by the proband is necessary.

 

Contact:

Responsible for  information & appointments: Manesi Amalia, Financial and administrative scientist

From Mondays to Fridays, times 10:00a.m. - 14:00 p.m.

Tel 210 7289118,288

FAX 210 7289289

emails:

  amaliam@med.uoa.gr

  gkaradim@med.uoa.gr

  gkoutsis@med.uoa.gr