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Congenital Myopathy via the HACD1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
15421 HACD1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15421HACD181479 81479,81479 $890 Order Options and Pricing

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Congenital myopathy (CM) refers to a genetically and clinically heterogeneous group of disorders characterized by muscle weakness and hypotonia at birth or in infancy. Five forms of congenital myopathy are recognized by the International Standards of Care Committee for Congenital Myopathies (North et al. 2014. PubMed ID: 24456932): nemaline myopathy, core myopathy, centronuclear myopathy, myosin storage myopathy, and congenital fiber type disproportion. The clinical course of congenital myopathy is typically static or slowly progressive. Lower facial weakness leading to an open mouth is often the first sign of congenital myopathy in the newborn. Ptosis and ophthalmoplegia are also common. See North et al. (2014) for diagnostic strategies and a comprehensive review of the congenital myopathies.

HACD1-related congenital myopathy has been reported in only about 5 families to date. All of the affected individuals were either homozygous or compound heterozygous for HACD1 variants, with several being clear loss-of-function variants. Clinical features include generalized muscle weakness, hypotonia, feeding problems, delayed motor milestones, facial weakness, and, in some cases, cardiac findings (Abbasi-Moheb et al. 2021. PubMed ID: 33354762). Genetic testing may aide in establishing a differential diagnosis and may assist reproductive planning.

Genetics

Pathogenic variants in the HACD1 gene are associated with autosomal recessive congenital myopathy. A splice variant, nonsense variant, missense variant, and 1250 bp LINE insertion in exon 6 have been reported in the HACD1 gene (Abbasi-Moheb et al. 2021. PubMed ID: 33354762; Al Amrani et al. 2020. PubMed ID: 32426512; Muhammad et al. 2013. PubMed ID: 23933735). To date, all pathogenic variants have been inherited from a carrier parent. No other large structural variants have been reported. HACD1 is relatively tolerant to loss of function variants (Genome Aggregation Database).

The HACD1 gene encodes 3-hydroxyacyl-CoA dehydratase 1, which is involved in the biosynthesis of very-long-chain fatty acids (VLCFAs). A SINE inserted in exon 2 of the canine HACD1 has been found to cause an autosomal recessive myopathy in Labrador retrievers, including hypotonia, generalized muscle weakness, reduced muscle mass, and exercise intolerance (Pelé et al. 2005. PubMed ID: 15829503). HACD1 has been cited as a non-essential gene for growth of human tissue culture cells (Online Gene Essentiality).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity is difficult to estimate as to date only a limited number of cases have been described in the literature (Abbasi-Moheb et al. 2021. PubMed ID: 33354762; Al Amrani et al. 2020. PubMed ID: 32426512; Muhammad et al. 2013. PubMed ID: 23933735). Analytical sensitivity should be high as almost all pathogenic variants reported to date are detectable by sequencing. A 1250 bp LINE insertion has been reported in exon 6 and it is uncertain if our NGS analysis would detect this variant (Al Amrani et al. 2020. PubMed ID: 32426512).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the HACD1 gene plus 10 bases flanking noncoding DNA in all available transcripts in addition to non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with clinical features consistent with a congenital myopathy. Targeted testing is indicated for family members of patients who have a known pathogenic variant in HACD1. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in HACD1.

Gene

Official Gene Symbol OMIM ID
HACD1 610467
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Abbasi-Moheb et al. 2021. PubMed ID: 33354762
  • Al Amrani et al. 2020. PubMed ID: 32426512
  • Genome Aggregation Database (gnomAD).
  • Muhammad et al. 2013. PubMed ID: 23933735
  • North et al. 2014. PubMed ID: 24456932
  • Online Gene Essentiality (OGEE).
  • Pelé et al. 2005. PubMed ID: 15829503

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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