Postnatal constitutional genetics – Eurofins Biomnis

Postnatal genetics examines the health of all individuals post-birth, as opposed to prenatal genetics. This means adults, children and infants are considered as well as newborns.

Pangenomic analyses (screening for genetic abnormalities across the entire genome)

Exome

For rare diseases, new diagnostic methods such as whole exome sequencing improve the speed and effectiveness of diagnosis.

This technique has been offered by Eurofins Biomnis since 2016 and can simultaneously sequence the coding regions of genes that can contain 95% of currently known mutations. With strong experience in this field, Eurofins Biomnis offers this examination for aetiological investigation of mental disorders, neurodevelopmental disorders or syndrome-based disorders, for clinical pictures that do not suggest screening for an abnormality in a gene or panel of genes (or if the results were negative for these tests), or where an organ is affected (kidney, heart, etc.).

The benefits of this approach are that all of the genes are studied simultaneously and the interpretation of the results can rapidly incorporate the latest medical discoveries.

Chromosomal microarray analysis (CGH array)

In postnatal genetics, chromosomal microarray analysis (SNP array) is recommended as a first-line investigation of neurodevelopmental disorders, facial dysmorphism or malformations. This pangenomic chromosome analysis can identify minute chromosomal imbalances that are difficult or impossible to identify using a karyotype or CNV (Copy Number Variation).

Eurofins Biomnis has SNP array (Single Nucleotide Polymorphism) technology, which in addition to being able to identify CNVs can identify regions of loss of heterozygosity (LOH).

Targets analyses (study of a gene or gene position)

In certain cases, clinical parameters allow the prescribing physician to suggest a targeted genetic study, of a specific gene or a specified gene position.

Genetics related to haematology and immunochemistry

Several areas of haematology are explored using techniques of molecular genetics.

In haemostasis, these techniques are used to study the constitutional factors that predispose an individual to venous thrombosis: factor V Leiden mutation, G20210A Factor II gene mutation and MTHFR mutations (c.677C>T and c.1298A>C).
The most common iron overload syndrome, Type 1 haemochromatosis, is diagnosed based on identification of a major C282Y mutation, and the minor H63D and S65C mutations, of the HFE gene.

Human leukocyte antigen (HLA) typing is performed to identify risk factors for several diseases. The most common associations investigated for HLA class I alleles are HLA B27/ankylosing spondylitis, HLA A29/birdshot retinopathy, HLA B51/Behcet’s disease, HLA B57:01/abacavir hypersensitivity. For class II HLA alleles, the most common associations are HLA DQ2 and DQ8/coeliac disease.

The SERPINA1 gene expressing alpha-1-antrypsin is investigated to identify the S and Z mutations because the ZZ and SZ genotypes are responsible for the low protein concentrations associated with emphysema or liver disease.

Pharmacogenetics

Pharmacogenetics consists of oncology and psychiatry, as part of personalised medicine.

Fluoropyrimidines (5-FU and capecitabine) are anti-cancer drugs and are included in close to 60% of chemotherapy protocols for a range of tumours (digestive tract, pancreas, breast, etc.), however these drugs have significant toxic effects, starting from the first course of treatment. This toxicity is linked to a deficit of the degradative enzyme for fluoropyrimidine: DPD. Testing for risk of fluoropyrimidines uses a multiparametric approach, combining genotyping and DPD phenotyping. In addition, when a risk of toxicity is identified, an adjustment is proposed for the dose of fluoropyrimidine to be used.
Moreover, screening for polymorphism of gene UGT1A1 helps with the diagnosis of Gilbert’s syndrome and can be used to estimate the risk of irinotecan toxicity, another anti-cancer drug, which is metabolised by the enzyme UGT1A1.

First-line treatment of depression is based, another other approaches, on antidepressants. For many antidepressants, diffusion in brain tissue is what determines their effectiveness, which is dependent on a protein, P-glycoprotein (P-gp), which is encoded by the gene ABCB1. Genotyping of ABCB1 allows the identification of the different forms of P-gp which reduce or promote passage of several antidepressants through the blood-brain barrier, which allows the treatment strategy to be adapted.

Oncogenetics

In France, close to 5% of cancer diagnoses are linked to the presence of constitutional genetic mutations. Individuals carrying these mutations are at a greater risk of developing cancer. Identifying this greater risk means that a screening programme, preventive measures and proactive, adapted treatments can be proposed.

The two genetic predispositions most frequently screened for are breast and ovarian cancer, and Lynch syndrome.

Infertility

In cases of infertility, the following screening may be performed in addition to the prescription of a karyotype:

  • For men, mutations of the mucoviscidosis gene (CFTR) and microdeletions of the Y chromosome.
  • For women, premutation of the FMR1 gene in cases of premature ovarian failure (early menopause).

Exome sequencing is also suggested with these indications.

Lactose intolerance

Primary lactose intolerance is linked to the absence or decreased production of lactase with age, responsible for degrading lactose, encoded by the LCT gene. Investigation of lactose intolerance includes screening for the presence of a 13910 C>T mutation on the LCT gene promoter, which allows lactase production sufficient for digestion of lactose to be maintained.

Neurological disorders

Fragile X syndrome can be screened for in cases of intellectual impairment in children or certain neurological diseases in adults. We also conduct screening for Prader–Willi syndrome and Angelman syndrome.

Other

In cases of suggestive clinical signs, we can also carry out screening for familial Mediterranean fever.

 

 
Document
B12-INTGB – Constitutional molecular genetics request form
Document
B34-INTGB – Exome request form
Document
B36-INTGB - Pharmacogenetic evaluation of the ABCB1 gene
Document
B61-INTGB – Cardiogenetics request form
Document
B67-INTGB - Oncogenetics - Hereditary predisposition to the occurrence of cancer
Document
D23-INTGB – Declaration of consultation and consent
Document
K23-24B-INTGB – Evaluation of the toxicity risk of fluoropyrimidines and determination of 5-fluorouracil
Document
R23-INTGB – Cystic fibrosis gene analysis (CFTR gene)
Document
R36-INTGB – Familial Mediterranean Fever gene study
Focus on
ABCB1 - Genetic testing to optimise the treatment of depression (DS45-INTGB) Genetic testing to optimise selection of antidepressants in the treatment of depression (DS45-INTGB-ABCB1)
Information for healthcare professionnals
Focus on
ABCB1 - Genetic testing to optimise the treatment of depression (DS74-INTGB-PA) Genetic testing to optimise selection of antidepressants in the treatment of depression (DS45-INTGB-ABCB1)
Information for patients
Focus on
Cardiomyopathies and arrhythmias (DS88-INTGB)
The contribution of cardiogénétcis in the management and care of patients and their families
Focus on
Chromosomal microarray analysis by SNP-array (DS21-INTGB)
Focus on
Gene panel SPINK1, PRSS1, CTRC, CPA1, CFTR et CASR for the diagnosis of hereditary pancreatitis (DS82-INTGB)
Focus on
Whole Exome Sequencing in genetic diseases (DS34-INTGB)

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