Genetica Molecolare | Genetics
Other Genetic Tests
Genetica Molecolare | Genetics
Other Genetic Tests
Genetica Molecolare | Genetics
Genetica Molecolare | Genetics
Genetica Molecolare | Genetics
Genetica Molecolare | Genetics
Massively parallel sequencing or Next Generation Sequencing (NGS) is an innovative and highly versatile technology that allows the parallel sequencing of millions of DNA fragments. This enables the simultaneous analysis of multiple genes, providing a higher diagnostic yield than traditional sequencing while significantly reducing turnaround time.
Next Lab Italy has implemented this technology by developing specific gene panels designed to investigate various pathological conditions and identify their genetic causes.
Gene panel sequencing generates a large volume of data, which may present challenges in terms of interpretation and management. It is generally recommended to confirm any mutation detected through NGS using Sanger sequencing.
In some cases, it may be necessary to establish the segregation of the mutation(s) in available family members.
The analysis may lead to three possible outcomes:
One or more genetic alterations are identified, which are interpreted as possible causes of the condition present in your family.
One or more genetic alterations are identified, but their role in relation to the condition is not clearly interpretable. In such cases, further investigations may be necessary to clarify the significance of these alterations. You will be informed of the results and kept up to date over time as interpretation evolves.
No relevant genetic alterations are identified to explain the condition under investigation. However, the results may be re-evaluated in the future as new information becomes available about the condition and the genes involved. You will be informed if relevant new findings emerge.
The test is performed at the Pavia operational site, which implements a quality management system in accordance with ISO 9001:2015 and SIGUCert standards
Cystic fibrosis (CF) is a genetic disorder characterised by high salt content in sweat and the production of thick, sticky mucus. It is the most common genetic condition among Caucasian children. Its incidence varies, being far less common among Asian and African populations than in Europe and North America. Prevalence in Europe is not known, but estimated at between 1 in 8,000 and 1 in 10,000 individuals.
Technology used:
F508del, I507del, F508C, I502T, 1706del17, 1677del TA, G542X, 1717-1G>A, R553X, Q552X, G551D, S549R(A>C), N1303K, 4016insT, R1162X, R1158X, W1282X, G1244E, 2789+5G>A, 2183AA>G, 711+5G>A, 711+1G>T, G85E, 3849+10kbC>T, 621+1G>T, R117H, D1152H, L1065P, R1066H, L1077P, 4382delA, 1259insA, 852del 22, R347P, T338I, S912X, A455E, 3199del6, D110H, G178R, R334W, R347H, R352Q, D579G, E585X, 1898+1G>A, 1898+3A>G, 2184insA, 3120+1G>A, 3272-26A>G, R1066C, 3659delC, G1349D, H139R, 1717-8G>A, 1874insT, 1898+5G>T, 2522insC, 4015delA, 991del5, M1V, D110E, R117C, 1078delT, 2143delT, L997F, F1052V, 1782delA, E193K, c.1584+18672 A>G. The test also includes analysis of polyT (5T/7T/9T) variants in IVS8 and following deletions: CFTR dele2ins182, CFTR dele1, CFTR dele22-23-24, CFTR dele22-23, CFTR dele2-3, CFTR dele17a-17b-18 and CFTR dele14b-17b.
Technology used:
This test, performed using NGS (Next Generation Sequencing) technology, analyses the entire coding sequence of the CFTR gene, intron-exon junctions, promoter, and selected clinically relevant intronic mutations. It also includes analysis of the polyT (5T/7T/9T) variants in IVS8.
Detection of the G1691A variant in the Factor V gene (Leiden variant)
Detection of the G20210A variant (Factor II)
Detection of the C677T/A1298C variants in MTHFR gene
Detection of the -675 4G/5G variants in PAI-1 gene
Detection of AZFa, AZFb, AZFc deletions
Detection of the ASN680SER variant in FSH-R gene
a C/T polymorphism at position c.-13910 in the regulatory region of the lactase (LCT) gene. The genetic test indicates whether a person is predisposed to develop a deficiency of the lactase enzyme (known as hypolactasia) later in life. If the C allele is present in both copies of the gene (homozygous), lactase production in the small intestine is reduced. People with T/C (heterozygous) or T/T (homozygous) genotypes usually produce enough lactase to digest lactose properly. The frequency of CC homozygotes is about 15–20% in Northern European populations and around 50% in some Mediterranean populations (such as Italians, Greeks, and Spaniards).
The genetic test for the c.-13910C>T variant in the LCT gene is considered an exclusion test. It helps rule out a genetic cause when symptoms appear after consuming lactose-containing foods. The test has a specificity and sensitivity greater than 99%.
The analysis consists of HLA gene typing and is a genetic susceptibility test that assesses an individual’s likelihood of developing coeliac disease, based on the presence or absence of risk factors (such as DQ2, DQ8). The presence of DQ2 and/or DQ8 alleles increases the risk of coeliac disease—up to 14 times higher than in the general population depending on the combination—whereas their absence makes the disease highly unlikely. DQ2 and DQ8 are heterodimeric glycoproteins on the surface of certain immune cells, made up of two chains (alpha and beta) which are encoded by DQA1 and DQB1 genes, respectively.
The DQA1*05 and DQB1*02 alleles encode the DQ2 heterodimer, which is associated with a higher risk of coeliac disease, while the DQA1*03 and DQB1*03:02 alleles encode the DQ8 heterodimer, associated with a lower risk. Among individuals with coeliac disease, over 80% have a DQ2 genotype (DQA1*05 and DQB1*02), 10% have a DQ8 genotype, and 5% are DQB1*02 positive but DQA1*05 negative. In rare cases (around 5%), coeliac disease can occur even in the absence of these genotypic combinations. HLA genes remain unchanged throughout life. The specificity and sensitivity of the genetic test are above 99%.
In the case of a positive result, it is strongly recommended to undergo an invasive test (intestinal biopsy), as HLA molecules alone are not sufficient to determine the presence of the disease. Coeliac disease only develops following exposure to specific environmental triggers and in the presence of additional genetic factors.
In males, the disease begins in childhood with delayed achievement of key developmental milestones. Cognitive impairment varies in severity. Behavioural disturbances may be mild or severe, and autistic-like behaviours may be present. In females, cognitive and behavioural symptoms are usually mild. At the beginning of the FMR1 gene, there is a repeated nucleotide triplet, the number of which can vary: – Individuals with fewer than 45 repeats do not develop Fragile X syndrome; – Individuals with 45 to 54 repeats (intermediate zone) do not develop Fragile X syndrome, but females have an increased risk of having children with further expansion; – Individuals with a premutation (55 to 200 repeats): females have an increased risk of having children with Fragile X syndrome; – Individuals with more than 200 repeats of the triplet develop Fragile X syndrome. Females may sometimes present with a mild form of the condition.
The genetic test determines the number of (CGG)n repeats in the 5′ untranslated region of the FMR1 gene, in order to distinguish between a healthy individual, a healthy carrier of a clinically significant expansion, and an affected individual.
mainly characterised by progressive gait and limb ataxia, dysarthria, dysphagia, oculomotor dysfunction, loss of deep tendon reflexes, pyramidal signs, scoliosis, and, in some cases, cardiomyopathy, diabetes mellitus, vision loss, and hearing impairment.