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Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome via the KCNH1 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
8081 KCNH1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8081KCNH181479 81479(x2) $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

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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Temple-Baraitser syndrome is a rare multisystem developmental disorder characterized by severe intellectual disability, epilepsy, dysmorphic facial features, and hypoplasia or aplasia of the nails of the thumbs and great toes (Jacquinet et al. 2010; Shen et al 2015; Simons et al. 2015).

Zimmermann-Laband syndrome is another rare developmental disorder characterized by facial dysmorphism including coarse face and gingival hypertrophy, hypoplasia or aplasia of nails and terminal phalanges, and hypertrichosis. Intellectual disability has been seen in patients (Kortum et al. 2015).

Temple-Baraitser syndrome and Zimmermann-Laband syndrome share not only the major feature of hypoplasia or aplasia of the nails of the thumbs and great toes, but also other minor characteristics.

Genetics

Both Temple-Baraitser syndrome and Zimmermann-Laband syndrome are inherited in an autosomal dominant manner. Temple-Baraitser syndrome is caused by pathogenic variants in the KCNH1 gene (Simons et al 2015), while Zimmermann-Laband syndrome is caused by pathogenic variants in the KCNH1 or ATP6V1B2 genes (Kortum et al. 2015). The reported KCNH1 pathogenic variants either in Temple-Baraitser syndrome or Zimmermann-Laband syndrome are missense variants. To date, large deletions or large duplications in KCNH1 have not been discovered (Human Gene Mutation Database).

KCNH1 encodes potassium channel, voltage gated EAG 1 related subfamily H, member 1 (Kv10.1). The gene is predominantly expressed in the adult central nervous system and is thought to be involved in neuronal activity, cell proliferation, and development. De novo pathogenic variants in KCNH1 occur in most cases (Simons et al. 2015). An in vitro study showed Temple-Baraitser syndrome associated pathogenic variants in KCNH1 leads to deleterious gain-of-function in potassium channel activity (Simons et al 2015). Another study also suggests a gain-of-function effect for all Zimmermann-Laband syndrome-associated KCNH1 pathogenic variants (Kortum et al. 2015). When a pathogenic variant in the KCNH1 channel was co-expressed with wild-type KCNH1, it formed heterotetrameric channels which reduced conductance at positive potentials, but also pronounced conductance at negative potentials.

Clinical Sensitivity - Sequencing with CNV PG-Select

KCNH1 is the only gene known to be involved with Temple-Baraitser syndrome. Compared to Temple-Baraitser syndrome, a molecular cause in KCNH1 was identified in 25% of cases with Zimmermann-Laband syndrome (Kortüm et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the KCNH1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

KCNH1 sequencing test is recommended for patients who are suspected to have Temple-Baraitser syndrome or Zimmermann-Laband syndrome.

Gene

Official Gene Symbol OMIM ID
KCNH1 603305
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Temple-Baraitser Syndrome AD 611816
Zimmermann-Laband Syndrome 1 AD 135500

Citations

  • Human Gene Mutation Database (Bio-base).
  • Jacquinet A. et al. 2010. American Journal of Medical Genetics. Part A. 152A: 2322-6. PubMed ID: 20683999
  • Kortüm F. et al. 2015. Nature Genetics. 47: 661-7. PubMed ID: 25915598
  • Shen J.J. 2015. Clinical Dysmorphology. 24: 55-60. PubMed ID: 25629734
  • Simons C. et al. 2015. Nature Genetics. 47: 73-7. PubMed ID: 25420144

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

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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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