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Autosomal Recessive Neurodevelopmental Disorder with Structural Brain Anomalies via the PTPN23 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
PTPN23 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13085PTPN2381479 81479,81479 $990 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 platform).

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

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


  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

Biallelic pathogenic variants in the PTPN23 gene cause an autosomal recessive syndromic disorder of neurodevelopmental delay and structural brain anomalies with or without seizures and spasticity (NEDBASS). Shared characteristics of affected individuals include developmental delay (100%), brain abnormalities (mainly ventriculomegaly and/or brain atrophy)(90%), intellectual disability (100%), spasticity (80%), language disorder (80%), microcephaly (60%), optic atrophy (50%), and seizures (50%). Many affected individuals remain completely nonverbal throughout life. Death during childhood (infection related) occurs in about 25% of the cases identified thus far. Features observed more rarely include developmental regression, tremor, contractures, apraxia, spastic diplegia, corpus callosum dysgenesis, dysmyelination, cerebellar atrophy, congenital heart defects, and hypotonia. Dysmorphic features are observed, but variable, and there is no recognizable facial gestalt. Shared dysmorphic features included prominent forehead, strabismus, prominent low-set or posteriorly rotated ears, broad nasal bridge and nasal tip, and broad mouth with full lips (Bend et al. 2020. PubMed ID: 31395947).

PTPN23-associated syndrome is thought to be a very rare neurodevelopmental disorder, with less than 20 patients currently identified. While there are currently no treatments, patients and their families may benefit from a molecular diagnosis for prognostic information, early identification and treatment of symptoms (such as seizures), or for connecting with relevant family support groups. For family planning, prenatal testing or pre-implantation genetic diagnosis may be implemented for future pregnancies.


PTPN23-associated neurodevelopmental delay with stuctural brain anomalies is an autosomal recessive disorder. Variant types cover a broad range including missense, in-frame deletions, nonsense, and frameshift variants. However, no patients have an allele combination predicted to result in complete loss of function of PTPN23, and this is likely incompatible with life. Both homozygous and compound heterozygous causative variants have been observed. None of the observed or reported variants are recurrent, and no large deletions or duplications (CNVs) have been reported as causative, to our knowledge.

Regarding genotype-phenotype correlations, phenotype may be more severe in patients with one loss of function (nonsense, frameshift) variant in trans with a missense variant. Pathogenic variants are widely spread across the protein, but missense changes do cluster in one of the protein's four functional domains. Many of the pathogenic variants are observed at a low frequency in gnomAD, up to 0.06%, or ~160 heterozygous individuals and 0 homozygous individuals. Some pathogenic missense variants may be causative only when observed in trans with a protein-terminating variant, but not in the homozygous state (Bend et al. 2020. PubMed ID: 31395947). PTPN23 is relatively intolerant to loss of function variants (Genome Aggregation Database).

PTPN23 encodes a 1636 amino acid protein-tyrosine phosphatase, implicated in ciliogenesis, the endosomal sorting complex required for transport (ESCRT) pathway, and RNA splicing. It is located on chromosome 3p21.3, and is composed of 24 exons. It is essential for embryonic development in mice, with knockout mice showing significant abnormalities and embryonic lethality around E9 (Gingras et al. 2009. PubMed ID: 19378249).  PTPN23 has been cited as a conditional gene for growth of human tissue culture cells (Online Gene Essentiality, ogee.medgenius.info).

Clinical Sensitivity - Sequencing with CNV PGxome

Due to the rarity of this syndrome, the diagnostic yield of this test for individuals with syndromic intellectual disability or developmental delay is predicted to be very low (<0.1%). Diagnostic yield is expected to be higher if several of the other defining features - such as brain atrophy, microcephaly, optic atrophy, or spasticity are observed. Still, it is important to note the high clinical and genetic heterogeneity of intellectual disability, and improved diagnostic yields that result from testing large panels of genes as well as testing parents along with the patient using a trio approach. The analytical sensitivity of this test is expected to be high, as it will detect all types of PTPN23 pathogenic variants identified to date.

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 PTPN23 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 coverage as ≥20X NGS reads or 2x Sanger sequencing.

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

This test is suitable for individuals with syndromic intellectual disability and developmental delay. Due to the high clinical and genetic heterogeneity of syndromic intellectual disability, testing for this gene could be included as part of a larger sequencing panel or exome test. Targeted testing is indicated for family members of patients who have known pathogenic variants in PTPN23. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PTPN23.


Official Gene Symbol OMIM ID
PTPN23 606584
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Bend et al. 2019. PubMed ID: 31395947
  • Genome Aggregation Database.
  • Gingras et al. 2009. PubMed ID: 19378249
  • Online Gene Essentiality (OGEE).


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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