The Invitae Immunodeficiency, Centromeric Instability, Facial Anomalies Syndrome Panel analyzes 2 genes that are associated with immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provide accurate risk assessment and carrier status for at-risk relatives.
For a broader analysis of the genetics of primary immunodeficiencies:
|Gene||Disorder||Protein name||Protein symbol|
|DNMT3B||Immunodeficiency with centromeric instability and facial anomalies (ICF1)||DNA methyltransferase 3B||DNMT3B|
|ZBTB24||Immunodeficiency with centromeric instability and facial anomalies (ICF2)||zinc finger and BTB-domain containing protein 24||ZBTB24|
ICF syndrome is characterized by the triad of agammaglobulinemia or hypogammaglobulinemia, centromeric instability and mild facial dysmorphism. Patients usually present with frequent infections due to immunodeficiency such as respiratory and gastrointestinal infections. These patients have reduced levels of IgA, IgG and/or IgM. T-cell numbers are decreased in roughly half of patients. Centromeric instability results in rearrangements adjacent to the centromeres of chromosomes 1, 16, and sometimes 9 in mitogen-stimulated lymphocytes. Mild facial dysmorphism can include a broad flat nasal bridge, hypertelorism, and epicanthal folds. Micrognathia, low set ears and macroglossia may also be present. At least one third of patients will have intellectual disability, psychomotor retardation, and slow cognitive development. Patients often die in childhood without treatment.
This panel is estimated to detect ~80% of patients with ICF syndrome.
|Gene||% cases attributed|
ICF syndrome is inherited in an autosomal recessive manner.
ICF syndrome is a rare disease and the exact prevalence is unknown.
This test may be appropriate for patients with:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|