About usThe Laboratory of Genome Diagnostics performs diagnostics for a large number of (rare) genetic disorders for both prenatal and postnatal genetic disorders. To guarantee the quality, Genome Diagnostics is accredited and is equipped with the latest state-of-the-art techniques and equipment. Read more
We offer a wide range of diagnostic genetic tests. The diagnostic tests are performed by an expert team of clinical geneticists laboratory specialists. Our laboratory uses a number of different methodologies and techniques including:
- DNA diagnostics, including exome sequencing, smMIP-technology, Sanger sequencing and MLPA analysis
- Molecular cytogenetics, including Array and FISH analysis
- Classic cytogenetics
- A full interpretation of any detected variant at DNA-level based on their biological and clinical significance
Our diagnostic department is specialised in identifying rare diseases, so please do not hesitate to contact us if you cannot find a specific test in our list.
Our laboratory has also dedicated itself to provide:
- The highest quality of service with competitive turnaround times and tariffs
- A high level of innovation, with efficient implementation of the newest methods and techniques whilst constantly expanding of our range of diagnostic services
Department of Genetics, division Genome Diagnostics
P.O. Box 9101, 6500 HB Nijmegen
Geert Grooteplein 10, 6525 GA Nijmegen
Opening hours: 24 hours a day
Telephone: +31(0)24 36 13799
Fax: +31(0)24 36 16658
Are there any current changes or limitations in place with regard to your molecular genetic diagnostic services?
We are currently working routine diagnostics as usual, with NO changes regarding turnaround times and patient samples. There may be a delay in the shipment time of samples, but that is depending on the countries involved.
Are you planning to actively communicate to requesting clinicians regarding future changes to your services?
We will communicate any significant changes due to the current global coronavirus situation through our website (https://order.radboudumc.nl/en/genetics), so please first look there for any announcements regarding our diagnostic services. Any correspondence regarding individual diagnostic requests will be communicated as usual, directly with the respective requesting clinician and/or lab scientist.
What are the details of online (website addresses) & other resources (e.g. auto-reply from a designated email), via which we can check ourselves for updated information re your services?
You can find all relevant information on our website (https://order.radboudumc.nl/en/genetics).
Do you have a list of appropriate contacts within your laboratory (name, email addresses and contact number), for use regarding clinically urgent case enquiries which we may have.
You can contact us as usual by sending an email to email@example.com or call us at +31 24 361 3799. For any specific inquiries, please ensure to mention any relevant (patient) information, phone and / or fax number in your email or message in case we need to contact you
The section genome diagnostics of the department of Genetics, and the translational metabolic laboratory of the department of laboratory medicine (both of the Radboudumc in Nijmegen) started in 2013, an intensive and far-reaching cooperation with the department of Clinical Genetics of the Maastricht UMC+.
Together we are able to offer a complete package of genetic and enzyme-/biochemical tests for both national and international physicians. We offer diagnostics for a large number of acuired, hereditary and/or congenital disorders. New tests are implemented in diagnostics after an extensive validation in accordance with current quality standards.
We have complementary expertise in both centers and we can jointly develop and implement the latest technologies. All genetic and enzyme-/biochemical tests of these two centers are offered in one and the same (this) ordering system, regardless of where the test is performed.
Turnaround times, materials and prices
|Service||Turnaround time (starting from receipt of material)||Required material||Price**|
|Exome sequencing diagnostics (WES)
||Exome gene panel analysis: 2-3 months||
- 2 x 3-6 ml EDTA blood (neonates 1x 1-2 ml)
- 20 ml amniotic fluid (only Rapid) or >30 ml (Rapid + QF-PRC + growing cells)
If there is no blood and/or amniotic fluid available:
- Desired amount DNA: >1 ug
Single WES analysis: €750
Trio WES analysis: €1550
Rapid single WES analysis: €2000
Rapid Trio WES analysis: €3000
|Exome gene panel analysis followed by exome wide analysis (in one report): 2-3 months|
|Rapid Trio/de novo analysis of proband and both parents: <15 business days|
|Interpretation of exome data||2 months||n/a||€400|
|Array diagnostics (genome wide)||5 weeks||2 x 3-6 ml EDTA blood (neonates 1x 1-2 ml)||€750|
|Multiple gene diagnostics (Gene panels)||3-8 weeks*||2 x 3-6 ml EDTA blood (neonates 1x 1-2 ml)||Please see our ordering system|
|Single gene diagnostics||4-8 weeks*||2 x 3-6 ml EDTA blood (neonates 1x 1-2 ml)||Please see our ordering system|
|4 weeks||Gene/array diagnostics: 2 x 3-6 ml EDTA blood (neonates 1x 1-2 ml)
Chromosome diagnostics (karyotyping):
2 x 5ml Heparine blood in Natrium- or Lithium-Heparine tubes (neonates 1x 1-2ml)
|Farmacogenetics||1-8 weeks*||2 x 3-6 ml EDTA blood||Please see our ordering system|
|Chromosome diagnostics||2-5 weeks||Karyotyping: 2 x 5 ml Heparine blood in Natrium- or Lithium-Heparine tubes (neonates 1x 1-2 ml)
QF-PCR: neonates: 1-2 ml EDTA blood or 1-2 ml Heparine blood in Natrium- or Lithium-Heparine tubes
|FISH||2-5 weeks||2 x 5 ml Heparine blood in natrium- of lithium-heparine tubes (neonates 1x 1-2 ml)||€750|
||Please, contact: firstname.lastname@example.org or
Tel: (024 36) 13799
TAT depends on technique
|Please, see material under requested service|
|mtDNA||4-12 weeks||Cooled (none frozen) urine, we prefer 50-100 ml||Please see our ordering system|
|Prenatal analysis||2-3 weeks||Please contact us via email@example.com||
Maternal cell contamination: €450
Known familial mutation: €320
Known familial mutation + Maternal cell contamination: €770
* In our ordering system you will find the exact turnaround time for each individual test.
** Upon cancellation the requested test will be charged completely.
Molecular analysis to detect pathogenic mutations in the exome.
More about Exome sequencing
Follow-up testing based on existing wes data.
More about Re-analysis of WES data
Re-analysis of WES dataIn the event that an whole exome application has been submitted for a single gene panel analysis, it is still possible to apply for another gene panel or an exome-wide analysis retrospectively. Existing data will receive a new analysis according to the latest scientific knowledge and panels.
For an exome-wide (open-exome) re-analysis, involvement of a clinical geneticist is needed for the application to facilitate a written ‘informed consent’ form for the patient. The clinical geneticist will also be responsible for saving the ‘informed consent’ form.
Molecular diagnostics of copy number variants (CNVs) and homozygous regions in the Human genome.
More about Array analysis (genome-wide)
Array analysis (genome-wide)
Within our department we annually perform 2500-3000 genome-wide array analyses for the detection of germline and acquired genomic abnormalities (Copy Number Variants (CNVs) and Regions Of Homozygosity (ROHs)).
We have two different array platforms from Thermo Fisher available:
The CytoScan HD array contains more than 2.6 million probes, including 750,000 single nucleotide polymorphism (SNP) probes, and we use this array to examine the patients’ DNA for CNVs and homozygous regions.
The CytoScan XON array contains almost 7 million probes, including 150,000 SNP probes, has excellent exon coverage and is therefore most suitable for the detection of intragenic CNVs, but this array can also be used for genome wide CNV analysis. If necessary, we will also examine the DNA of the respective parents (to perform so called patient-parent trio analysis).
Please note that as of 2022 in most cases the CNV detection will be performed by exome wide CNV analysis in Whole Exome Sequencing data instead of genome wide array analysis. This exome wide CNV in exome data analysis is a validated, good and efficient alternative with a comparable diagnostic yield compared to genome wide array analysis. Furthermore, it is possible in one test to analysis and interpret both CNVs as well as nucleotide variants either simultaneously or sequentially. Nucleotide variants are always first analysed using one or multiple gene panels, depending on the reason for referral.
The array is employed for many indications including:
- Multiple congenital disorders
- Intellectual disabilities
- ‘Homozygosity mapping’ as a screening tool
- Carrier testing in an unaffected individual
- Validation / segregation analysis for intragenic CNVs (instead of MLPA)
- Ultrasound anomalies (see also Prenatal diagnostics)
- Intra uterine foetal death (see also Prenatal diagnostics)
- Hemato-oncological disorders (ALL, CLL, MM, MPN, MDS) (see Tumour genetics)
Using our Electronic Application System you can request for array diagnostics. The system also includes all information regarding shipping instructions and the expected turn-around times.
Please order array diagnostic requests for hemato-oncological disorders (ALL, CLL, MM, MPN, MDS) using the form of our Tumour Genetics Laboratory.
Besides WES we also offer gene panels with a shorter turnaround time and full coverage of the exons including the intron-exon limits.
More about Gene panels
These following gene panels are widely used in diagnostics using single molecular Molecule Inversion Probes (smMIPs) or Ion Torrent technology, sometimes in combination with Sanger sequencing and MLPA-analysis:
- Breast- and ovarian cancer-panel (smMIPs)
- Cardiomyopathy (smMIPs, conducted by our partner MUMC+)
- Kidney cancer-panel (smMIPs)
- Paraganglioma-panel (smMIPs)
- Paraganglioma/Pheochromocytoma -panel (smMIPs)
- Polyposis-panel (smMIPS)
By making an application through our Electronic Application System you will be able to see which genes per gene panel are tested, the expected turnaround times and shipping instructions. We also offer various gene panels/exome panels via whole exome sequencing.
We offer molecular diagnostics for more than 1200 single genes.
More about Single gene analysis
Single gene analysisPer gene, a specific test is performed, ensuring that the coded area and the intron-exon boundaries are comprehensively covered. Depending on which gene it is, a MLPA-analysis might also be performed. Using our Electronic Application System you can see if we offer a specific test for your gene of interest, if that particular gene is part of an existing panel, which biological samples need to be shipped for the test and what the expected turnaround time is. For variant(s) that are identified by whole exome sequencing and for which targeted gene analysis is unavailable, we can offer carrier screening for the relevant variant(s).
Testing for a family known mutation or a known chromosome abnormality.
More about Familial mutation
Familial mutationWhen performing familial mutation screening, several different tests are used by our diagnostics department. We will often make use of Sanger sequencing as a test, but other frequently used test methods are single molecule Molecular Inversion Probes sequencing, fragment analysis, array analysis, chromosome analysis, MLPA and/or deletion PCR. The expected turnaround times for carrier screening is 4 weeks.
In prenatal carrier screening, we work with different turnaround times (see prenatal diagnostics). Ot note, prenatal carrier screening for gene defects also requires a biological sample from the mother in order to exclude the possibility of maternal cell contamination.
For presymptomatic carrier screening in children younger than 18 years, the involvement of a clinical geneticist is a requirement.
By using our application form you can apply for carrier screening for a specific gene mutation or chromosome abnormality.
Within our diagnostics we offer general chromosome diagnostics to identify numerical and structural abnormalities by means of karyotyping and / or QF-PCR.
More about Chromosome analysis
Chromosome analysisChromosome analysis is performed for a number of indications, including:
- Habitual abortion
- Suspicion of down syndrome
- Abnormal sexual development, including the suspicion of Turner syndrome or Klinefelter syndrome
- Breakage syndromes such as Nijmegen breakage syndrome, Bloom syndrome, Fanconi anaemia, and ataxia telangiectasia. (please note that due to the necessary preparations needed for a chromosome breakage analysis, please consult with the secretariat before sending samples (firstname.lastname@example.org)
- Carrier screening for family members in case of a known chromosome disorder.
- Echoscopical disorders (including, suspicion of triploidy, Edwards syndrome, Patau syndrome, Down syndrome)
- Hemato-oncological disorders (please note that these applications go through The Tumour Genetics Laboratory)
Targeted chromosome analysis for identification of chromosomal aberrations by means of Fluorescence In Situ Hybridization (FISH).
More about FISH
FISHFacilitated by the presence of a large collection of FISH-probes we are able to conduct targeted chromosome analysis to identify chromosomal abnormalities. FISH can be performed on dividing cells (which can be extracted from heparin blood, amniotic fluid, chorionic or skin biopsy), also known as metaphase-FISH. It is also possible to conduct FISH on non-dividing cells (e.g. obtained from the mucus membrane in the cheek), also known as interphase-FISH. We do however have a preference for analysis on dividing cells.
FISH is used for several indications within genome diagnostics. FISH can be used for the following:
- A known chromosomal translocation in a family
- In a supplementary role to confirm/exclude the existence of a numerical or structural chromosomal abnormality found using array analysis or karyotyping
- If there is a suspicion of (low) mosaic (sex) chromosomal disorder (such as Turner syndrome and Klinefelter syndrome)
Fields of Interest
In a few hospitals (the Network Prenatal Diagnostics Nijmegen), prenatal testing is performed on fetal material obtained via invasive or non-invasive methods.
More about Prenatal testing
A number of hospitals in the region of Nijmegen are working closely together in the fields of prenatal screening, diagnostics and therapy. They have created the Prenatal Diagnostic Network Nijmegen (NPDN). This unique collaboration in the South-East of the Netherlands provides prenatal diagnostics of the highest level by joining forces to not only gather knowledge, but also to implement and transfer knowledge. At the heart of this network is the Radboudumc. The surrounding hospitals function as ‘satellites’, with Radboudumc performing all diagnostic procedures in their laboratories. The NPDN comprises of the following hospitals:
- Arnhem, Rijnstate Hospital
- Den Bosch, Jeroen Bosch Hospital
- Ede, Gelderse Vallei Hospital
- Enschede, Twente Medical Spectrum
- Nijmegen, Radboudumc
- Tilburg, St. Elisabeth Hospital
- Tilburg, Tweesteden Hospital
The application forms are not available online.
Invasive prenatal testing
Invasive tests are performed either on chorionic villus sampling (CVS, placental cell sample) or amniocentesis material (amniotic fluid sample).
Indications for invasive diagnostic testing
Below you will find a list of indications for taking a placental cell sample or taking an amniotic fluid sample:
- Pregnant females at higher risk of giving birth to a child with Down syndrome, Edwards syndrome, or Patau syndrome, following a combination test.
- Pregnant females who have (repeatedly) given birth to children with a chromosomal disorder.
- (Prospective) parents, one of whom, has a chromosomal disorder.
- Pregnant females, who after having a ultrasound examination, are shown to be carrying a foetus with a congenital anomaly.
- Pregnant females at higher risk of (a) an autosomal dominant genetic alteration, (b) an autosomal recessive metabolic defect or (c) an inherited X-linked chromosomal condition.
- Pregnant females with a hereditary mitochondrial condition.
- Pregnant females who have previously given birth to a child with congenital disorder and thus carry a higher risk of chromosomal abnormality.
- Pregnant females who have already had a CVS or amniocentesis for (an)other indication(s), but who still might have testing performed for chromosome abnormalities, without having to have additional procedures to obtain biological samples from the foetus.
- Pregnant females with a conflicting NIPT test result.
- NB the indication: "Pregnant females who are in the 18th week of their pregnancy at 36 years of age" is no longer in effect, as of 1 January 2015.
- CVS (QF-PCR analysis) numerical disorders in chromosomes 13/18/21/X/Y: 24-72 hours
- CVS , comprehensive karyotyping: 10 days
- Amniocentesis (amniotic fluid sample), (QF-PCR-test) numerical disorders in chromosomes 13/18/21/X/Y: 24-72 hours
- Amniocentesis (amniotic fluid sample), comprehensive karyotyping: within 3 weeks
- CVS and Amniocentesis (amniotic fluid sample), Array analysis: within 3 weeks
- Prenatal DNA analysis performed, due to an increased risk of an autosomal dominant, autosomal recessive or X-linked hereditary disorder: 2-3 weeks
- Exomesequencing using prenatal material (rapid exome): <3 weeks
The prenatal diagnostic group is headed by Dr. Dominique Smeets.
Within tumour genetics, a distinction is made between inherited tumours and acquired tumours such as hemato-oncological disorders. This results in two separate application routes.
More about Tumor genetics
Tumour geneticsThe Tumour Genetics Laboratory (LTG) provides molecular diagnostics within the field of oncology. These diagnostics are aimed at detecting germline mutations that lead to a genetic predisposition for developing certain types of tumour. The LTG also specializes in the detection of tumour specific changes that have been acquired. These changes are of particular importance for differential diagnosis, predicting outcomes or therapy responses.
Applications in relation to hereditary tumours (germline mutations) can be submitted using the application system of the genome diagnostics department. By typing the applicable test (e.g. the name of the gene) more information will be provided regarding the expected test result, shipping instructions and whether the relevant gene is present in a gene panel.
Applications in relation to acquired tumours such as haemato-oncological diseases can be submitted to the Tumour Genetics Laboratory.
The Tumour Genetics Laboratory is headed by prof. dr. Marjolijn Ligtenberg.
Both genome-wide assays as well as targeted analysis are used to identify the genetic causes explaining the clinical features of patients with Intellectual/Congenital or Endocrine disorders.
More about Intellectual Disabilities and Congenital Disorders
Intellectual Disabilities and Congenital DisordersWithin the group ‘Intellectual Disabilities & Congenital Disorders’ both genome-wide assays as well as targeted analysis are used to identify the genetic causes explaining the clinical features of patients with Intellectual Disabilities and/or Congenital Disorders or endocrine disorders. The group concerns itself with all patients, of all age groups from new-borns to the elderly, and with a diverse range of clinical indications.
With the exception of genome-wide SNP-based array analysis for the detection of causal CNVs (copy number variants) the majority of analyses is whole exome based, involving the detection of de novo mutations using ‘patient-parent trio analyses’. Additional analysis is performed to find causal recessive and X-linked chromosomal disorders. Determining the cause of a genetic disorder is of great importance to (extended) families who run a higher risk of recurrence. This is not only importance for recessive, and X-linked chromosomal disorders, but also for families where one parent is carrier of a balanced chromosomal rearrangement, a mosaic mutation, or a genetic mutation as a result of an imprinting defect, all of which can cause varying clinical consequences. The discovery of the underlying mechanism responsible for causing the genomic disorder will enable better counselling for all parties concerned and help further determine the recurrence risk.
Our team has particular expertise in the field of genetic causes of Intellectual disabilities (Dr. R. Pfundt and Dr. N. de Leeuw), craniofacial anomalies (Dr. R. Pfundt) and endocrine conditions (Dr. T. Rinne).
The research group for Intellectual Disabilities & Congenital Disorders is headed by Dr. Nicole de Leeuw.
We offer a comprehensive package of genetic and functional tests for the diagnosis of muscular-, neurological-, kidney and sensory disorders.
More about Muscular-, neurological-, kidney diseases and sensory disorders
Muscular-, neurological-, kidney diseases and sensory disorders
Muscular disordersMuscular disorders consists of number of muscular diseases (e.g. Atrophy, Dystrophy, Myopathy, Myotonia and Muscle weakness) and abnormalities of the neuromuscular system (i.a. Myasthenic syndromes). Diagnostic analysis usually involves a combination of whole exome sequencing, with a primary focus on the genes implicated in Muscular disorders. Targeted gene analysis is possible when dealing with clinically recognisable Muscular disorders with little locus heterogeneity. Muscular disorders caused by repeat expansions (such as Myotonic Dystrophy) will also be subject to targeted analysis.
Neurological disordersThe majority of diagnostic analysis is concentrated on Cerebellar Ataxia, Spastic Paraplegia, Dystonia, and Epilepsy. The analysis itself usually involves a combination of whole exome sequencing with a primary analysis of the genes implicated in Neurological disorders. Targeted gene analysis is possible when dealing with clinically recognisable Neurological disorders with little locus heterogeneity. Syndromes caused by repeat expansions (such as the dominant SCAs) will also be subject to targeted analysis. Scientific research into Cerebellar Ataxia, Spastic Paraplegia and Dystonia will be performed at the centre of expertise for movement disorders. Research into Intellectual disabilities is classified as a separate field of research.
Hearing LossHereditary deafness, or hearing impairment, can be congenital or develop at an older age. There is also a clear distinction between perceptive (sensorineural) deafness (caused by a problem in the inner ear, the vestibulocochlear nerve and/or parts of the brain) and conductive (middle ear) deafness (caused by a problem with the outer ear and/or middle ear). A combination of perceptive and conductive deafness is also possible. In addition, syndromes can occur in which hearing loss is accompanied by other health problems, with Usher syndrome being perhaps the most well-known example.
Diagnostic analysis usually involves a combination of whole exome sequencing, possibly preceded by a single gene analysis if a single gene is known to harbour many mutations for the disease or syndrome in question (e.g. GJB2 for congenital deafness). Scientific research into hereditary deafness is conducted as part of a collaboration with a centre of expertise “Hearing and Genes”.
We offer a large variety of genetic and functional tests for the diagnostics of Metabolic and Mitochondrial diseases.
More about Hereditary Metabolic and Mitochondrial diseases
Hereditary Metabolic and Mitochondrial diseasesWe offer a large variety of genetic tests for the diagnostics of Metabolic and Mitochondrial diseases. Additionally, we also have a comprehensive set of functional assays that can not only be requested prior to genetic diagnostics, but also for further functional follow-up for variants of unknown clinical significance.
Not all drug therapies have the same effect on every individual. Sometimes a medication will deliver the desired result, on other occasions there might be side-effects or no results at all.
More about Pharmacogenetics
PharmacogeneticsWhat is pharmacogenetics?
Not all drug therapies have the same effect on every individual. Sometimes a medication will deliver the desired result, on other occasions there might be side-effects or no results at all, meaning that an alternative therapy has to be found. The differences in reaction to drug therapies have a varied set of underlying causes.
Known causes include environmental factors, such as smoking and diet, co-medication or an underlying medical condition. There is however a large percentage of causes that are the result of a genetic predisposition. Only a limited number of genes is involved in drug metabolisms. The primary aim of Pharmacogenetics is to identify which variants in those genes modulate drug response.
Medicines made to measure
Pharmacogenetic diagnostics play a large role in providing therapy perfectly suited to the needs of the individual patient. Testing for known variants that have an effect on the metabolic pathways of medication before starting therapy, is helpful in predicting the reaction to therapy. A genetic variant can cause a medication to be metabolized at a slower rate, increasing the chance of side-effects. A variant can also cause an increased rate of metabolism which means that the medicine does not remain in the body long enough to have an effect, or alternatively, severely decreases the effect of the medicine. By having tests performed beforehand, you know what you can expect from your therapy. The prevention of side-effects is better than curing them!
The Genomics Technology Center ensures that high quality data is delivered with short turnaround times for our diagnostic tests and tests intended for research.
More about our Genomics Technology Center
Clinical information, diagnostics and research come together in Translational Genomics to bring about concrete healthcare innovation in the field of clinical genetics.
More about Translational genomics
Translational genomicsWe now have a research group specialized in putting new insights into clinical and diagnostic practice, called “translational genomics”. Within this group, there is a lot of attention given to the clinical utility technology and diagnostic strategy, but there is also a lot of consideration for if the aforementioned can be optimised for more routine applications. There is also careful consideration for the advantages that can be found, compared with more traditional methods when looking at diagnostic success, the costs of health care and patient satisfaction.
The research group for Translational Genomics is headed by Dr. Lisenka Vissers.
Our bioinformatics group provides analyzes for large and/or complex data for genetic diagnostics within Radboudumc.
More about Bioinformatics
BioinformaticsWithin the Bioinformatics group, there are a number of different fields of expertise such as: data management, software-development and -design, automation, server management en statistical methodology.
The group conducts a number of routine analyses including:
- Analysis of whole exome sequencing (WES) data for diagnostic purposes (alignment, variant calling, de novo mutation detection, CNV detection, annotation and quality control)
- Analysis of Molecular Inversion Probe (MIP) data (alignment, variant calling, CNV detection, annotation and quality control)
- Analysis of whole genome sequencing (WGS) data (alignment, variant calling, de novo mutation detection)
- Support for microarray diagnostics
- Analysis of long read technologies (Pacific Biosciences Sequel technology)
- Analysis of RNA-sequencing (transcriptome) data
- Analysis of data from metabolomic experiments
The group for Bioinformatics is headed by Dr. Christian Gilissen.
The Laboratory of Genome Diagnostics has state-of-the-art techniques and equipment. In the Competency Statement is described how the laboratory guarantees its quality. In this competency statement the scope and operation list of the laboratory are included.
To guarantee the quality, Genome Diagnostics is accredited for ISO 15189_2012 (accreditation number M100) and participates in the relevant quality assessment programs (since 2001) of the EMQN, GenQA, CEQAS and CF Network (see certificates for past two years). Genome Diagnostics is registered on the website of Orphanet.
- Certificate accreditation ISO15189_2012 (English)
- Competency Statement
- Cystic Fibrosis Certificate 2020
- Cystic Fibrosis Certificate 2021
- EMQN Certificate 2020
- EMQN Certificate 2021
- GenQA Performance certificate 2020
- GenQA Performance certificate 2021
For comments or questions, please contact our Quality team.