recessive gene test

231 carrier screening tests developed by the Medicover Genetics Ltd. laboratory.
Genomic deoxyribonucleic acid (gDNA) is extracted using standardized methods and mechanically fragmented prior to DNA library preparation.
DNA enrichment of the genomic region of interest is performed using solution-based hybridization methods and sequenced next-generation sequencing (NGS).
The readout sequence data is referenced to a reference genome and mutations are identified using a proprietary bioinformatics pipeline.
Recessive inheritance can be identified in single nucleotide variants, small insertions and deletions (≤30 bases) and copy number variations (CNV).
Variants are classified according to the American College of Medical Genomics and Genomics 3-5 criteria.
Variant classification and interpretation is performed using the Varsome Clinical platform and is based on information available at the time of inspection.
Only pathogenic and suspected pathogenic mutations are reported. Detected but unidentified variants of unknown significance, benign or possibly benign variants will not be reported.
Only pathogenic and suspected pathogenic mutations will be reported. Mutants of unknown significance that have been detected but not identified, and benign or possibly benign mutants will not be reported.
A: If the autosomal result is
A-1: "No clinically significant variants detected."
While it is not a complete guarantee that the subject is not a carrier of a genetic disease, it does indicate the absence of a genetic mutation and says that the likelihood of being a carrier is low.
A-2: "Clinically significant variants detected."
A genetic change is identified, indicating that the subject is a carrier of the disease.
In such cases, they can be carriers of two or more diseases.
Carriers usually do not have symptoms of the disease.
However, it is possible that both genes of the two chromosomes show abnormalities, in which case the possibility that the subject is currently affected or will be in the future cannot be ruled out.
B: For X-linked hereditary diseases:
B-1: "No clinically significant variants detected."
The absence of a hereditary variant indicates that the subject is not affected if the subject is male, and the possibility of carrier is small if the subject is female, but does not completely rule out the possibility of carrier.
B-2: "Clinically significant variants detected":
Indicates that a genetic alteration has been identified and other In the case of female subjects, it is possible that they are carriers.
If the subject is male, it indicates that he is currently affected or may develop the disease in the future.
However, the disease groups in this panel vary in severity and may not present clinically.
The purpose of the test is to detect all variants associated with the detected gene by targeting all coding exons, MANE and/or standard transcripts, and 10 bp of adjacent intronic sequences.
Mutants outside the target region are not intended to be detected by this assay.
Unless otherwise noted, sequence changes (SNVs and INDELS) in promoters and other non-coding regions are not detected in this assay.
Certain sequence changes (SNVs and INDELS) in non-coding regions of the detected gene that are considered clinically important are included in the analysis.
When two variants are identified in a gene, it is not possible to distinguish whether they are on one chromosome (cis) or another (trans).
Genetic changes such as inversion, rearrangement, ploidy, and epigenetic effects are not covered by this test.
Certain sequence variations (SNVs and INDELS) in target regions, including repetitive sequences, highly homologous sequences such as segmental duplications and pseudogenes, and regions of high/low GC content may not be detected.
Copy Number Variations (CNVs) are calculated using high-quality sequencing reads that are free of duplicates and uniquely aligned.
Using GC content normalization and depth of sequencing range approach, CNVs are detected for a subset of target regions.
CNV anomalies are detected when the detected COVERAGE deviates significantly from the COVERAGE estimated from the reference site.
CNV detection is possible down to a few exon-level resolutions.
If the CNV is positive, the orthogonal method is used to confirm the results.
Genomic regions that contain little or no mapping, repetitive sequences, pseudogenes, or high/low GC content will not detect CNV.

The absence of a reported CNV does not guarantee that the CNV is not present, since the detection of CNVs using NGS is less sensitive/specific than the orthogonal quantification method.
The fact that no disease-causing variants are present in the target gene decreases the likelihood of disease, but does not completely eliminate the possibility of disease-related syndromes.
Alpha-thalassemia, spinal muscular atrophy and fragile X syndrome are performed using the methods described below.

• Alpha Thalassemia:.
  Deletion/duplication analysis of the alpha-globin (HBA) gene cluster (HBZ, HBM, HBA2, HBA1 and HBQ1) and its HS-40 regulatory region is performed by multiple linkage dependent amplification (MLPA) using MRC holland probemix P140, which covers over 90% of affected cases.
  The assay also checks for the presence of Constant Spring Mutation.
  This analysis does not detect other variants of the alpha globin gene or variants of the beta globin gene that can cause disease.
  Certain breakpoints or large deletions/duplications will not be detected.
  Individuals with both deletions and duplications within the alpha gene cluster may appear to have a normal number of alpha-globin copies.
  False positives and false negatives may result from technical or rare forms of alpha thalassemia or rare biological reasons.
• Spinal muscular atrophy:.
  To detect copy number changes in exons 7 and 8 of the SMN1 gene, MLPA analysis will be performed using the SALSA MLPA probemix P060.
  The test also detects copy number changes in exons 7 and 8 of the SMN2 gene as an interpretive aid for SMN1 copy number determination.
  This test does not detect SMA cases caused by de novo mutations.
  Chromosome phases of SMN1 and SMN2 copies are not detected. The test does not detect "silent carriers," individuals with one or more SMN1 copies on one chromosome and zero copies on the other chromosome.
  False positive and false negative results may occur due to rare sequence mutations, regulatory region mutations, copy number mutations, intron mutations, rare technical reasons, or other rare biological reasons.
• Fragile X Syndrome:.
  Isolated DNA is amplified by polymerase chain reaction (PCR) to determine the number of CGG repeats within the FMR1 gene.
  PCR products are generated using fluorescently labeled primers and sized by capillary gel electrophoresis.
  Interpretation is based on the number of iterations in the iterated array below.
  Negative:<44
  Intermediate:45~54
  Possible mutation: 55~200
  Complete mutation:>200
  Since Southern blotting is not performed, cases exceeding 200 may not be accurately detected.
  In addition, methylation status has not been analyzed.
  Rare genetic variants, mosaicism, blood transfusions, bone marrow transplants, and other rare molecular events can produce false positive or false negative results.
  The development and performance evaluation of the recessive genetic carrier screening test was performed by Medicover Genetics Ltd. which is qualified to perform high complexity under the Clinical Laboratory Improvement Act of 1998 (CLIA).
  The development and performance evaluation of the recessive genetic carrier screening test was conducted by Medicover Genetics Ltd. which is qualified to perform high complexity under the Clinical Laboratory Improvement Act of 1998 (CLIA).

• ・NM_000383.4 (AIRE): exon 1
• ・NM_000414.4 (HSD17B4): exon 5
• ・NM_001352514.2 (HLCS): exon 1
• ・NM_013339.4 (ALG6): exon 13
• ・NM_014244.5 (ADAMTS2): exon 1
• ・NM_025114.4 (CEP290): exons 5, 23
• ・NM_000233.4 (LHCGR): exon 1
• ・NM_001384140.1 (PCDH15): exons 33, 34, 35
• ・NM_153818.2/NM_002617.4 (PEX10): exon 1
• ・NM_032520.5 (GNPTG): exon 1
• ・NM_000521.4 (HEXB): exon 4
• ・NM_000232.5 (SGCB): exon 1
• ・NM_020533.3 (MCOLN1): exon 1
• ・NM_152419.3 (HGSNAT): exon 1.

Validation testing is performed by Medicaver Genetics Ltd.
The test does not identify all mutations associated with the disease tested.
Although the test is extremely accurate, the possibility of false positive or false negative results still exists and can be caused by technical or biological limitations.
They include rare genetic variants, mosaicism, blood transfusions, bone marrow transplants, or other rare molecular events.
Some genetic alterations that are not detected may be affected and are not tested by the carrier screening test.
Although genetic testing is an important part of the diagnostic process, genetic testing does not always provide definitive answers. In some cases, a genetic mutation may be present, but the test may not identify it.
This is due to limitations in current medical knowledge or testing techniques.
Concurrent use of other clinical data and clinical findings is recommended.
The outcome results should always be considered in the context of other clinical findings.
The clinician who referred the patient for testing is responsible for pre- and post-test counseling, including advice regarding the need for additional genetic testing.
Other diagnostic tests may be required.