The Invitae Cohen syndrome test analyzes VPS13B (also known as COH1), a gene associated with Cohen syndrome, a multisystem disorder characterized by developmental delay, intellectual disability, microcephaly, hypotonia and truncal obesity.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.
Cohen syndrome is a developmental disorder characterized by intellectual disability, microcephaly, hypotonia, joint hypermobility, characteristic facial features, short stature, progressive early onset myopia, progressive retinochoroidal dystrophy, neutropenia and truncal obesity developing in late childhood. Affected individuals are described as having a happy disposition. The features of Cohen syndrome can vary widely between individuals.
Approximately 88% of patients with a strong clinical suspicion of Cohen syndrome have homozygous or compound heterozygous pathogenic variants in VPS13B.
Cohen syndrome is inherited in an autosomal recessive manner.
Cohen syndrome is a highly penetrant condition with variable expressivity.
An exact prevalence of Cohen syndrome is not yet known. It has been diagnosed in fewer than 1,000 people worldwide.
This test could be considered for patients who present with six or more of the following criteria (PMID: 15141358):
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|