Our Services

Single Gene Analysis

We use Sanger sequencing for small-scale applications in cases of a clear, clinically defined indication of a monogenic disease with an associated gene defect, or to identify individual familial disease-causing genetic variants through targeted analysis. For large genes or when further analysis is required, next-generation sequencing (NGS) may be used. Single Gene Diagnostics for genetically heterogeneous disorders. It is used when a specific genetic disorder is suspected. To look at sequencing of the full coding region of a single gene with intron/exon boundaries.

Methods

  • Sanger sequencing
  • Next-generation sequencing (NGS)

Exome Sequencing Analysis

It provides exome sequencing as an addition to our phenotype-driven panel diagnostics. In cases where a phenotype-based gene panel and other molecular genetic testing have not resulted in a diagnosis, exome sequencing may be the next option of choice. Exome analysis is recommended in cases of suspected hereditary diseases which cannot be clearly assigned to a genetic syndrome or even narrowed down to potential mutations based on clinical features. A clinical exome involving the healthy parents of an affected patient (trio analysis) can, in particular, also be a good possibility to uncover a suspected de-novo mutation.

Tests Available

The Clinical Exome and Whole Exome to supplement its extensive catalog of phenotype-based gene panels.

Clinical Exome Analysis

The Clinical Exome, which is a more straightforward analysis in routine clinical genetic testing, currently includes simultaneous next-generation sequencing (NGS) analysis of 3,963 disease-relevant genes with an associated phenotype in OMIM and Orphanet which at the same time are known in RefSeq and UCSC (except mtDNA).

This disease-oriented analysis offers a number of advantages over the analysis of the complete exome or even of the genome. In addition to lower costs and shorter turnaround time, the clinical exome enables easier interpretation of data as well as significantly higher coverage of disease-relevant genes. This greatly increases the probability of detecting the genetic cause of a patient’s symptoms.

Whole exome sequencing encompasses enrichment and sequencing of all exons of the genome, which are the protein-coding genes (~ 20,000 genes), and is suited for patients, whose diagnosis could not be confirmed by clinical exome investigation.

Methylation Analysis

Methylation analysis provides important information about the inactivation and regulation of DNA sections, associated with various disorders, which might go undetected when using only sequencing analyses or fragment length-based techniques.

Methods

We use one or more of the following methods for determining methylation status:
  • Methylation-sensitive MLPA (MS-MLPA)
  • Methylation-sensitive restriction analysis

Mutation Diagnostics (Carrier Testing)

We offers two types of mutation diagnostics:
1- carrier testing of known mutation(s) in family members
2- (prenatal) carrier testing of known mutation(s) in (unborn) fetus

Familial mutation testing includes:
-Sequencing a specific part of a given gene
- Full clinical interpretation of mutations within a comprehensive report

Prenatal carrier testing includes:
-Sequencing a specific part of a given gene
-Molecular testing of maternal cell contamination (MCC)
-Full clinical interpretation of mutations within a comprehensive report

Deletion/Duplication Analysis

A significant number of rare genetic diseases are caused by gene dosage abnormalities. Even small imbalances (deletions or duplications) can cause a clinically conspicuous phenotype. These copy number variations (CNVs), such as complete or partial deletion/duplication of single or multiple genes, can be detected by specific techniques and might otherwise go undetected, using standard gene sequencing analyses.

A significant number of rare genetic diseases are caused by gene dosage abnormalities. Even small imbalances (deletions or duplications) can cause a clinically conspicuous phenotype. These copy number variations (CNVs), such as complete or partial deletion/duplication of single or multiple genes, can be detected by specific techniques and might otherwise go undetected, using standard gene sequencing analyses.

Tests Available & Methods

We offers deletion/duplication analysis for different syndromes and disorders.
Some of the more common applications include:
  • Predisposition to Cancer
  • Neuromuscular Disorders
  • Intellectual Disabilities
  • Solid Tumors
Efficient and sensitive methods that serve as a detection system for the loss and/or gain of genomic regions and are incorporated as standard technologies in our laboratory include:
  • Next-generation sequencing (NGS)
  • Multiplex ligation-dependent probe amplification (MLPA) analysis, and Chromosomal microarray analysis (CMA).

Next-Generation Sequencing (NGS)

We offers NGS testing for deletions/duplications of important genes/gene fragments with every gene panel. The method tests all coding exons plus exon/intron borders (+/- 5 bp) for point mutations and small insertions/deletions, to approximately 50 bp.

Dosage analysis using NGS represents one method for the detection of copy number variations (CNVs) and single nucleotide variants (SNVs) within a gene panel or single gene. Depending upon the clinical details of a patient, an additional dosage analysis using MLPA or CMA may be required.

Genes for which a dosage analysis is included in our phenotype-based gene panels can be seen by viewing the associated test details.

MLPA Analysis

MLPA is the preferred method of analysis for the detection of large genomic deletions or duplications (>50 bp).

MLPA testing for genomic deletions and duplications is included in the following diagnostics:

  • BRCA1, BRCA2
  • Duchenne/Becker-Kiener Muscular Dystrophy (Test ID 20)
  • Hereditary Nonpolyposis Colon Cancer/Lynch Syndrome (Test ID 99)
In cases of gene panels with individual regions of insufficient coverage, MLPA deletion/duplication testing may be suggested as an option for further analysis.

Chromosomal Microarray Analysis (CMA)

The MGZ offers CMA for the detection of pathogenic copy number variants (CNVs). This high-resolution method is particularly useful for the following indications:
  • Developmental delay
  • Multiple congenital anomalies
  • Intellectual disability
  • Autism spectrum disorders
Turnaround Time
  • 3–6 weeks
  • 2-4 weeks (targeted analysis only)

General Sample Requirements

DNA (50 ng/µl)

Preferred quantity: 10 µg (minimum required: 3 µg)
Packaging: It is best to use a DNA tube with a screw cap. DNA tubes without screw caps should be sealed with paraffin film to prevent leakage.

EDTA blood

Preferred quantity: 4 ml (minimum required: 2 ml)
Packaging: Shatterproof. Please use Monovettes® (from Sarstedt) or Vacutainers® (Becton Dickinson) without a separating gel.

Peripheral heparinized blood (either lithium or sodium heparin)

Preferred quantity: 4 ml (minimum required: 2 ml)
Packaging: Shatterproof. Please use Monovettes® (from Sarstedt) or Vacutainers® (Becton Dickinson) without a separating gel.

Peripheral heparinized blood (either lithium or sodium heparin)

Preferred quantity: 4 ml (minimum required: 2 ml)
Packaging: Shatterproof. Please use Monovettes® (from Sarstedt) or Vacutainers® (Becton Dickinson) without a separating gel.

Newborns, and umbilical cord blood

Preferred quantity: >1 ml (minimum required: 0.5 ml) heparinized blood (either lithium or sodium heparin)
Packaging: Shatterproof. Please use Monovettes® (from Sarstedt) or Vacutainers® (Becton Dickinson) without a separating gel.

Prenatal Samples

Unless maternal cell contamination is excluded by another laboratory, we highly recommend sending us a maternal EDTA blood or blood-DNA sample for all prenatal molecular genetic analyses.

Cell-free fetal DNA (cffDNA) is fetal DNA

Fetal DNA which circulates freely in the maternal blood

Chorionic villus sampling (CVS)

Either 10-20 mg chorionic villi in a tube with sterile transport media, or 1-2 sterile confluent T25 flask(s) of cultured CVS cells

Amniotic fluid (AF)

Either 5-15 ml amniotic fluid in a tube with sterile transport media, or 1-2 sterile confluent T25 flask(s) of cultured amniotic fluid cells

Cytogenetics And Microarray Analysis

Chromosomal Microarray Analysis (CMA)

CMA is particularly useful in cases of developmental delay, multiple congenital anomalies, intellectual disability, and autism spectrum disorders.
CMA is a first-tier assay for the identification of pathogenic copy number variants. Employing 850K BeadChip (Illumina) allows for high resolution testing of copy number variants and of copy number neutral regions of loss of heterozygosity (LOH), as well as low-level mosaicism (up to 10%).

Sample Requirements

Accepted Sample Types
  • 2-4 ml EDTA blood or DNA
  • Prenatal samples (amniotic fluid, chorionic villus sampling)
  • Products of conception (POC)

Karyotyping

Karyotyping of GTG-banded metaphase chromosomes is applied to test for numerical (aneuploidies) and structural chromosome aberrations (balanced and unbalanced).
Indications for karyotyping include:
  • Suspicion of numerical or structural chromosome aberrations
  • Infertility / subfertility
  • Recurrent miscarriages
  • Family history of chromosome aberration
  • Mosaicism
  • Prenatal testing

Sample Requirements

Accepted Sample Types
  • 2-4 ml heparinized peripheral blood
  • Prenatal samples (amniotic fluid, chorionic villus sampling)
  • Skin biopsies
  • Products of conception (POC)

Turnaround Time

  • 2 weeks
  • 4 days (if urgent)

Fluorescent in-situ Hybridization (FISH)

Fluorescent in-situ-hybridization (FISH) is offered in the frame of prenatal aneuploidy testing, and to validate results of karyotyping and CMA assays.
FISH utilizes fluorochrome-labeled probes that bind to complementary chromosomal regions.
Sample Requirements
Accepted Sample Types
  • 2-4 ml heparinized peripheral blood
  • Prenatal samples (amniotic fluid, chorionic villus sampling)
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