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  • Test code: 01737
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae RECQL4-Related Disorders Test

Test description

This test analyzes the RECQL4, a gene that is associated with three distinct conditions: Rothmund-Thomson syndrome (RTS), Baller-Gerold syndrome (BGS), and RAPADILINO syndrome. These syndromes are each characterized by a specific presentation, but they have overlapping features, including radial ray defects, skeletal abnormalities, slow growth/short stature, and an increased risk for malignancy.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (1 gene)
  • Baller-Gerold syndrome (BGS)
  • RAPADILINO syndrome
  • Rothmund-Thomson syndrome (RTS)

RECQL4-related conditions are diagnosed early in life and are characterized by radial ray defects, skeletal abnormalities, and slow growth and short stature. Three distinct syndromes are associated with RECQL4, including:

Rothmund-Thomson syndrome (RTS)
Characterized by poikiloderma (sparse hair, eyelashes, or eyebrows), small stature, skeletal and dental abnormalities, cataracts, and an increased risk for osteosarcoma
Baller-Gerold syndrome (BGS)
Characterized by coronal craniosynostosis with ocular proptosis and bulging forehead, radial ray defects, aplasia or hypoplasia of the radius, growth restriction, and poikiloderma
RAPADILINO syndrome
An acronym for radial ray defect; patellae hypoplasia or aplasia and cleft or highly arched palate; diarrhea and dislocated joints; limb malformation; nose slender and normal intelligence; characterized by pre- and postnatal growth restriction

  • RTS – The prevalence of osteosarcoma was 30% in affected individuals, with a median age at diagnosis at 11 years. There is also an increased risk of basal cell carcinoma and squamous cell carcinoma.
  • BGS – An increased risk for osteosarcoma, lymphoma, and skin cancer was reported.
  • RAPADILINO syndrome – An increased risk for osteosarcoma during childhood or adolescence and for lymphoma in young adulthood.

All RECQL4-related conditions reported to date have an autosomal recessive inheritance pattern.

The prevalence of RECQL4-related conditions is currently unknown.

Analysis of the RECQL4 gene may be considered in individuals with the following (major findings):

  • poikiloderma in infancy
  • coronal craniosynostosis
  • radial ray defects/short stature
  • positive family history of RECQL4-related 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 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
RECQL4 NM_004260.3