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Hyperphenylalaninemia via the DNAJC12 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
11879 DNAJC12 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11879DNAJC1281479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Phenylketonuria (PKU) and deficiencies of tetrahydrobiopterin (BH4) metabolism are inborn errors of metabolism that are associated with hyperphenylalaninemia (HPA) (Blau et al. 2014; Regier and Greene 2017). Deficiencies of BH4 metabolism are also associated with deficiencies in the neurotransmitters dopamine and serotonin (Blau et al. 2014). Recently, six individuals with clinical and biochemical features suggestive of either PKU or a BH4 metabolic defect were reported from four unrelated, consanguineous families. However, none of these individuals harbored pathogenic variants in genes previously known to be associated with these disorders. Whole exome sequencing (WES) revealed homozygous sequence variants in the DNAJC12 gene in all six individuals (Anikster et al. 2017).

Five of the six individuals were symptomatic before a diagnosis was made. All of the symptomatic patients exhibited a movement disorder that was similar to that observed in individuals with BH4 metabolic deficiencies, and was the reason they were brought to clinical attention. These patients exhibited HPA, though their urinary pterin measurements and DHPR activity from dried blood spots showed no evidence of a BH4 metabolic defect. However, analysis of the cerebrospinal fluid (CSF) revealed deficiencies of dopamine and serotonin, as well as an elevated homovanillic acid/5-hydroxyindoleacetic acid (HVA/HIAA) ratio (Anikster et al. 2017).

All patients were treated with BH4, with or without L-Dopa/carbidopa/5-hydroxytryptophan. Patients were reported to show a favorable response to treatment, particularly if treatment was started early. The authors suggest that all individuals with HPA, no causative variants in the PAH gene, and negative screening results for a BH4 metabolic defect should have genetic analysis of the DNAJC12 gene performed (Anikster et al. 2017).

Genetics

Current knowledge about DNAJC12-associated hyperphenylalaninemia deficiency suggests that this is an autosomal recessive disorder (Anikster et al. 2017). To date, one gross deletion, one missense variant, and one splice variant have been reported.

The DNAJC12 gene encodes a heat shock co-chaperone family member protein, which has been shown to interact with the phenylalanine, tyrosine and tryptophan hydroxylases.

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity is difficult to estimate because only a small number of patients have been reported. Based on the currently reported patients, analytical sensitivity may be ~50%, as half of the families reported in the literature were found to have gross deletions that may not be detectable via direct sequencing (Anikster et al. 2017).

Testing Strategy

This test provides full coverage of all coding exons of the DNAJC12 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other 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

Patients with hyperphenylalaninemia, no causative variants in the PAH gene, negative urinary screening results for a BH4 metabolic defect, and potentially a movement disorder are good candidates for this test. CSF screening results may show an elevated HVA/HIAA ratio. Family members of patients who have known DNAJC12 pathogenic variants are candidates. We will also sequence the DNAJC12 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
DNAJC12 606060
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hyperphenylalaninemia, Mild, Non-BH4-Deficient AR 617384

Related Tests

Name
6-Pyruvoyltetrahydropterin Synthase (PTPS) Deficiency via the PTS Gene
Dihydropteridine Reductase (DHPR) Deficiency via the QDPR Gene
Hyperphenylalaninemia Panel
Phenylalanine Hydroxylase Deficiency via the PAH Gene
Sepiapterin Reductase (SR) Deficiency via the SPR Gene

Citations

  • Anikster Y. et al. 2017. American Journal of Human Genetics. 100: 257-266. PubMed ID: 28132689
  • Blau N.et al. 2014. Disorders of Tetrahydrobiopterin and Related Biogenic Amines. Online Metabolic & Molecular Bases of Inherited Disease, New York, NY: McGraw-Hill.
  • Regier D.S. and Greene C.L. 2017. Phenylalanine Hydroxylase Deficiency. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301677

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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