Primary Ciliary Dyskinesia Panel

Content Review: May 2021 Last Update:
  • Use to detect variants in genes related to primary ciliary dyskinesia, which can present with laterality defects such as situs inversus or heterotaxy as well as pulmonary disease.
  • Regions of low coverage and reported variants are confirmed by Sanger sequencing as necessary.

Primary ciliary dyskinesia (PCD), also known as Kartagener syndrome, is a rare inherited condition that results from an underlying defect in the structure or function of motile cilia, impacting multiple body systems. Patients with PCD typically first present with neonatal respiratory distress, chronic oto-sinopulmonary disease, and year-round wet coughing. Chronic airway infection in patients with PCD often leads to bronchiectasis and obstructive lung disease, and hearing loss (either transient or permanent) can result from recurrent ear infection. Approximately half of patients with PCD will have a laterality defect such as situs inversus totalis or heterotaxy (refer to the Heterotaxy and Situs Inversus Panel Test Fact Sheet). PCD is also associated with infertility and ectopic pregnancy due to ciliary dysfunction.

Disease Overview

Prevalence

Approximately 1 in 16,000

Genetics

Etiology

Pathogenic variants in genes related to structure and function of the motile cilia

Penetrance

100%

Inheritance

Autosomal recessive; rare X-linked recessive forms have been reported

Test Interpretation

Clinical Sensitivity

Variable; dependent on phenotype/condition

Analytic Sensitivity

For massively parallel sequencing:

Variant Class Analytic Sensitivity (PPA) Estimatea (%) Analytic Sensitivity (PPA) 95% Credibility Regiona (%)

SNVs

99.2

96.9-99.4

Deletions 1-10 bp

93.8

84.3-98.2

Deletions 11-44 bp

99.9

87.8-100

Insertions 1-10 bp

94.8

86.8-98.5

Insertions 11-23 bp

99.9

62.1-100

aGenes included on this test are a subset of a larger methods-based validation from which the PPA values are derived.

bp, base pairs; PPA, positive percent agreement; SNVs, single nucleotide variants

Limitations

  • A negative result does not exclude a diagnosis of primary ciliary dyskinesia.
  • Diagnostic errors can occur due to rare sequence variations.
  • Interpretation of this test result may be impacted if this patient has had an allogeneic stem cell transplantation.
  • The following will not be evaluated:
    • Variants outside the coding regions and intron-exon boundaries of targeted genes
    • Regulatory region and deep intronic variants
    • Noncoding transcripts
    • The following exons are not sequenced due to technical limitations of the assay:
      • ARMC4(NM_001290020) exon 9
      • ARMC4(NM_001290021) exon 13
      • ARMC4(NM_001312689) exon 4
      • ARMC4(NM_018076) exon 9
      • CCDC103(NM_001258397) exon 4
      • CCDC114(NM_001364171) exon 3
      • CCDC114(NM_001364171) partial exon 4(Chr19:48822049-48822069)
      • CCDC40(NM_001243342) exon 18
      • CFAP298(NM_001350335) partial exon 5(Chr21:33975399-33975450)
      • CFAP298(NM_001350337) partial exon 6(Chr21:33974534-33974561)
      • DNAAF5(NM_017802) exon 1
      • DNAI2(NM_001353167) exon 13
      • SPAG1(NM_001374321) partial exon 11(Chr8:101225456-101225529)
      • SPAG1(NM_003114) partial exon 11(Chr8:101225456-101225529)
      • SPAG1(NM_172218) partial exon 11(Chr8:101225456-101225529)
  • The following may not be detected:
    • Deletions/duplications/insertions of any size by massively parallel sequencing
    • Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions
    • Low-level somatic variants

Genes Tested

Gene Name MIM # Associated Disorder Inheritance Pattern

ARMC4

615408

PCD

AR

CCDC103

614677

PCD

AR

CCDC114

615038

PCD

AR

CCDC151

615956

PCD

AR

CCDC39

613798

PCD

AR

CCDC40

613799

PCD

AR

CCDC65

611088

PCD

AR

CCNO

607752

PCD

AR

CFAP298

615494

PCD

AR

DNAAF1

613190

PCD

AR

DNAAF2

612517

PCD

AR

DNAAF3

614566

PCD

AR

DNAAF4

608706

PCD

AR

DNAAF5

614864

PCD

AR

DNAH1

603332

PCD

AR

DNAH11

603339

PCD

AR

DNAH5

603335

PCD

AR

DNAI1

604366

PCD

AR

DNAI2

605483

PCD

AR

DNAL1

610062

PCD

AR

DRC1

615288

PCD

AR

GAS8

605178

PCD

AR

LRRC6

614930

PCD

AR

MCIDAS

614086

PCD

AR

NME8

607421

PCD

AR

PIH1D3

300933

PCD

XLR

RSPH1

609314

PCD

AR

RSPH3

615876

PCD

AR

RSPH4A

612647

PCD

AR

RSPH9

612648

PCD

AR

SPAG1

603395

PCD

AR

ZMYND10

607070

PCD

AR

AR, autosomal recessive; XLR, X-linked recessive