Test code: 10004

Achalasia: Sequencing Panel
Test Code: 10004
Turnaround time: 6 weeks

Condition description

Achalasia is a disorder of the esophagus, in which the esophagus has abnormal muscle activity and does not possess the ability to move food into the stomach. The major symptom is usually difficulty with swallowing. Complications may include regurgitation, gastroesophageal reflux, pulmonary aspiration, and perforation of the esophagus. Achalasia affects approximately 1 in every 100,000 people in the United States.

The etiology of achalasia remains largely unknown; however, the occurrence of familial achalasia and its association with defined genetic syndromes have indicated that in some cases achalasia can be caused by genetic anomalies. CEN4GEN tests for genes known to cause the following achalasia-associated syndromes:

  • Triple A syndrome (Achalasia-Addisonianism-Alacrima) or Allgrove syndrome
  • Moyamoya diesase-6 with achalasia
  • Alacrima, achalasia, and mental retardation syndrome
  • Baraister-Winter Cerebrofrontofacial syndrome
  • Autoimmune Polyendocrine syndrome type with or without Reversible Metaphyseal dysplasia
  • Ataxia, posterior column, with retinitis pigmentosa (PCARP)

References:
1. MedlinePlus: https://www.nlm.nih.gov/medlineplus/ency/article/000267.htm
2. Dumic M et al. Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome. Eur J Pediatr. 2012 Oct;171(10):1453-9. Epub 2012 Apr 28.
3. OMIM

GENES
AAAS, ACTB, AIRE, FLVCR1, GMPPA, GUCY1A3

INDICATIONS

This test is indicated for:

  • Individuals with a clinical diagnosis of achalasia.

METHODOLOGY

Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

DETECTION

Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.

Analytical Sensitivity: ~99%

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types

* Preferred specimen type: Whole Blood

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.