Invitae Ligase IV Syndrome Test


Test description

The Invitae Ligase IV Syndrome Test analyzes LIG4, which is the primary gene associated with ligase IV syndrome (LIG4). LIG4 is a rare disorder characterized by developmental and growth delays, recurrent infections, and predisposition to cancer. Genetic testing can confirm a diagnosis, guide an individual’s medical management, help predict disease progression and outcome, and indicate the recurrence risk.

Order test

Primary panel (1 gene)


Ligase IV syndrome (LIG4)

Ligase IV syndrome (LIG4) is a progressive multisystemic disorder characterized by physical abnormalities, immunodeficiency, and cognitive impairment. Physical abnormalities can include microcephaly, growth retardation, distinctive facial features, and skin anomalies. Immunodeficiency is caused by a reduced production of blood and immune cells, leading to low blood cell counts (pancytopenia) and resulting in recurrent infections. Individuals with LIG4 also have an increased risk of developing malignancies, including leukemias and lymphomas. The clinical phenotype of LIG4 syndrome overlaps with other rare DNA damage response diseases such as Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia.

Due to the extreme rarity of this disorder, the clinical sensitivity of this test has not been determined.

LIG4 is inherited in an autosomal recessive pattern.

LIG4 is a highly variable disease. The severity of the phenotype is dependent on the pathogenic variant detected. Due to the increased sensitivity to ionizing radiation, an increased risk for malignancy is expected, though the lifetime risk has not been defined.

The prevalence of LIG4 is unknown.

Genetic testing for LIG4 can be helpful for patients with features of DNA damage repair disorders.

Assay and technical information

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
LIG4 NM_002312.3