Bohring-Opitz Syndrome via the ASXL1 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
9827 ASXL1 81175 81175,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9827ASXL181175 81175, 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Intellectual Disability (ID) is a heterogeneous group of neurodevelopmental disorders, characterized by congenital limitation in intellectual functioning (intelligence quotient, IQ ≤70), and adaptive behavior. It is diagnosed in ~1–3% of the population before 18 years of age (American Association of Intellectual and Developmental Disabilities, AAIDD).

Bohring-Opitz syndrome (BOPS), also known as Oberklaid-Danks syndrome or C-like syndrome, is a form of syndromic ID that is caused by the deficiency of a transcription regulator, Additional Sex Combs Like 1 (ASXL1) protein. Clinical features of BOPS vary and may include (but may not be limited to) developmental delay, speech and language delay, intellectual disability, seizures, epilepsy, hypotonia, structural brain malformations such as Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosum, short stature, intrauterine growth retardation, failure to thrive, feeding difficulties, gastroesophageal reflux, microcephaly, coarse facies, dysmorphic features including brachycephaly, triangular and hypotonic face, micrognathia, prominent forehead, retrognathia, facial hemangioma, low-set posteriorly rotated ears, hypertelorism, epicanthus, upslanting palpebral fissures and other abnormalities of the head, neck, chest, skin, nails, hair, ocular, cardiovascular, genitourinary and skeletal systems (Bohring et al. 2006. PubMed ID: 16691589, Pierron et al. 2009. PubMed ID: 19606480, Avila et al. 2013. PubMed ID: 23704076, Magini et al. 2012. PubMed ID: 22419483). Of note, early childhood deaths have been reported in severely affected individuals (Hoischen et al. 2011. PubMed ID: 21706002).

Genetics

Bohring-Opitz syndrome (BOPS) is an autosomal dominant disorder, caused by heterozygous pathogenic variants (primarily de novo) in ASXL1. ASXL1 consists of 14 coding exons and maps to chromosome 20q11.21, encoding a 1541 amino acid polypeptide. ASXL1 is a putative polycomb group protein and acts on homeobox (Hox) genes as a repressor as well as an enhancer, and is important for development. Although the function of the ASXL-gene family in human development is largely unknown, in Drosophila Asx regulation is highly variable and tightly controlled directly after fertilization (Russell and Graham. 2013. PubMed ID: 23672984). ASXL1 is known to repress the transcription of a subset of adipogenic genes and to regulate adipogenesis primarily via peroxisome proliferator-activated receptor (PPAR)-gamma (Park et al. 2011. PubMed ID: 21047783). Of note, complete knock out mice model of Asxl1 showed embryonic lethality (~80%) during late gestation as well as developmental abnormalities, dwarfism, anophthalmia and similar features of myelodysplastic syndrome (MDS) (Wang et al. 2014. PubMed ID: 24255920). To date, nonsense, missense, frameshift and splice site pathogenic variants have been reported and there are also reports of gross duplications involving ASXL1 (Human Gene Mutation Database). The disease transmission pattern is consistent with autosomal dominant inheritance.

Testing Strategy

This test provides full coverage of all coding exons of the ASXL1 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect pathogenic variants in <0.1% of individuals with intellectual disability (ID). In this context, it is important to note that although pathological variants over 800 genes have been identified in individuals with ID, a genetic diagnosis is still lacking in most cases due to extreme clinical and genetic heterogeneity of the condition (Vissers et al. 2016. PubMed ID: 26503795). We expect the analytical sensitivity for detection of nucleotide substitutions and small insertions or deletions to be high.

To date, three gross duplications involving ASXL1 have been reported (Avila et al. 2013. PubMed ID: 23704076).

Indications for Test

Targeted Sanger sequencing in ASXL1 is appropriate for the family members of patients with ASXL1 pathogenic variants. Of note, a panel (or exome/genome) sequencing test would nearly always be more appropriate for patients with intellectual disabilities, unless clinical knowledge clearly implicates the ASXL1 gene. Prenatal testing is possible only if the genetic diagnosis has been firmly established in an affected family member.

Gene

Official Gene Symbol OMIM ID
ASXL1 612990
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Bohring-Opitz Syndrome AD 605039

Citations

  • Avila et al. 2013. PubMed ID: 23704076
  • Bohring et al. 2006. PubMed ID: 16691589
  • Hoischen et al. 2011. PubMed ID: 21706002
  • Human Gene Mutation Database (Bio-base).
  • Magini et al. 2012. PubMed ID: 22419483
  • Park et al. 2011. PubMed ID: 21047783
  • Pierron et al. 2009. PubMed ID: 19606480
  • Reuter et al. 2017. PubMed ID: 28097321
  • Russell and Graham. 2013. PubMed ID: 23672984
  • Vissers et al. 2016. PubMed ID: 26503795
  • Wang et al. 2014. PubMed ID: 24255920

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.

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 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.

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