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CerebroTendinous Xanthomatosis (CTX) via the CYP27A1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7881 CYP27A1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7881CYP27A181479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Cerebrotendinous xanthomatosis (CTX) is rare lipid storage disease with accumulation of cholestenol and cholesterol in most tissues such as bile and brain. Elevated levels of cholestenol in these tissues leads to a variable clinical presentation that often includes chronic diarrhea, cataracts, pyramidal signs, neurological dysfunction marked by dementia, spinal cord paresis, progressive cerebellar ataxia, and multiple xanthomas of tendons and other tissues (Cali et al. 1991. PubMed ID: 2019602; Berginer et al. 2009. PubMed ID: 19117873; Cruysberg et al. 1995. PubMed ID: 7485361; Di Taranto et al. 2016. PubMed ID: 27225395). Variability in phenotype is a significant barrier to diagnosis. For example, identical adult twins have presented with considerable differences in the severity of phenotype (Zádori et al. 2017. PubMed ID: 27888347).

Infantile-onset chronic diarrhea may be the earliest clinical manifestation of CTX and followed by childhood-onset cataract, adolescent to young adult-onset tendon xanthomas, and adult-onset progressive neurologic dysfunctions (dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, dystonia, atypical parkinsonism, peripheral neuropathy, and seizures) (Federico et al. 1993. PubMed ID: 20301583). A study of the clinical course, genotypes and metabolic background in 175 patients with CTX observed that the incidence of tendon xanthomas was 71%, cataracts was 92%, low intelligence was 81%, and other neurologic symptoms 100% (Moghadasian. 2004. PubMed ID: 15061585). Less commonly, seizures, osteoporosis, coronary artery disease, premature atherosclerosis and Parkinsonism have been reported (Berginer et al. 2009. PubMed ID: 19117873; Gallus et al. 2010. PubMed ID: 20402754

Early diagnosis of CTX is essential as many of the clinical manifestations of this disease may be prevented by administration of chenodeoxycholic acid (CDCA) (Keren and Falik-Zaccai. 2009. PubMed ID: 19696711; Berginer et al. 2009. PubMed ID: 19117873). CDCA treatment after disease progression appears to be less effective.

The prevalence of CTX is estimated at 3 to 5 per 100,000 (Lorincz et al. 2005. PubMed ID: 16157755).


CTX is a rare autosomal recessive inborn error of bile acid synthesis due to markedly diminished activity of the mitochondrial enzyme sterol 27-hydroxylase (CYP27). The CYP27 enzyme is encoded by CYP27A1 located on the long arm of chromosome 2. CYP27 is responsible for the conversion of cholesterol to cholic and chenodeoxycholic acid. Almost all the causative variants in CYP27A1 lead to the absence of or the inactive form of CYP27 enzyme and altered urinary bile acid composition (Moghadasian. 2004. PubMed ID: 15061585; Gallus et al. 2006. PubMed ID: 16816916).

Although CTX is rare disorder worldwide, high frequency genetic islands have been reported (Keren and Falik-Zaccai. 2009. PubMed ID: 19696711). Some pathogenic variants have relatively high frequency in some ethnic groups such as p.Thr339Met (alternatively defined as p.Thr306Met) in Dutch patients, different substitutions for Arg479 amino acid (alternatively defined as Arg446) in Japanese and Sardinia patients and p.Ala216Pro (alternatively defined as p.Ala183Pro) in Italian cases (Gallus et al. 2006. PubMed ID: 16816916).

Knock-out mice model studies suggest that disruption of the CYP27 (Sterol 27-Hydroxylase) gene results in markedly reduced bile acid synthesis, but maintained levels of cholesterol and vitamin D metabolites (Rosen et al. 1998. PubMed ID: 9614081). CYP27A1 has been cited as a conditional gene for growth of human tissue culture cells (Online Gene Essentiality, ogee.medgenius.info). CYP27A1 is relatively tolerant to loss of function variants (Genome Aggregation Database).

So far, over 100 CTX causative variants (missense/nonsense, splicing, small and gross insertions/duplications) have been reported in CYP27A1 (Human Gene Mutation Database). Copy number variants are less frequently reported in this gene.

In one study, ~41% of all the patients with CTX had causative variants in the region of exons 6 to 8 This region encodes for adrenodoxin and haem binding sites of the protein (Verrips et al. 2000. PubMed ID: 10775536). No de novo variants in this gene have been reported to date.

Clinical Sensitivity - Sequencing with CNV PG-Select

CYP27A1 causative variant screening in patients identified pathogenic variants in 63 out of 64 alleles, which indicates that it is unlikely that another gene is involved in the pathogenesis of CTX (Verrips et al. 2000. PubMed ID: 10775536).

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 CYP27A1 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.

Indications for Test

Children presenting with chronic diarrhea and juvenile cataracts are candidates. Targeted testing is indicated for family members of patients who have known pathogenic variants in CYP27A1. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CYP27A1.


Official Gene Symbol OMIM ID
CYP27A1 606530
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Cerebrotendinous Xanthomatosis AR 213700


  • Berginer et al. 2009. PubMed ID: 19117873
  • Cali et al. 1991. PubMed ID: 2019602
  • Cruysberg et al. 1995. PubMed ID: 7485361
  • Di Taranto et al. 2016. PubMed ID: 27225395
  • Federico et al. 1993. PubMed ID: 20301583
  • Gallus et al. 2006. PubMed ID: 16816916
  • Genome Aggregation Database (gnomAD).
  • Human Gene Mutation Database (Bio-base).
  • Keren and Falik-Zaccai. 2009. PubMed ID: 19696711
  • Lorincz et al. 2005. PubMed ID: 16157755
  • Moghadasian. 2004. PubMed ID: 15061585
  • Rosen et al. 1998. PubMed ID: 9614081
  • Verrips et al. 2000. PubMed ID: 10775536
  • Zádori et al. 2017. PubMed ID: 27888347


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

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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.
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