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Genitourinary and/or Brain Malformation Syndrome (GUBS) via the PPP1R12A 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
13323 PPP1R12A 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13323PPP1R12A81479 81479,81479 $890 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 backbone).

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

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

  • Erin Sybouts, PhD

Clinical Features and Genetics

Clinical Features

Genitourinary and/or brain malformation syndrome (GUBS) is a congenital disorder primarily characterized by genitourinary anomalies and/or brain abnormalities. Major characteristics include developmental delay, brain malformations, and genitourinary (GU) malformations. Reported brain malformations include holoprosencephaly, corpus callosum abnormalities, anencephaly, absent septum pellucidum, and neuronal migrations defects such as polymicrogyria and heterotopia. The reported GU malformations include micropenis, chordee, hypospadias, cryptorchidism, and persistent Müllerian duct. Minor features can include dysmorphic facial features, omphalocele, and eye anomalies such as strabismus, esotropia, visual impairment, nystagmus, astigmatism and hyperopia (Hughes et al. 2020. PubMed ID: 31883643).

As this is a recently described disorder that shares phenotypic overlap with a number of other congenital disorders, it is difficult to estimate the incidence of GUBS; however, it is expected to be rare.

Advantages of testing for variants in PPP1R12A include molecular confirmation of a clinical diagnosis and identification of de novo variants in known or suspected cases. In general, larger panel testing is recommended for identifying an unknown genetic cause in developmental delay and brain malformation cases.

Genetics

GUBS is caused by heterozygous variants in the PPP1R12A gene. All disease causing variants reported thus far have been de novo loss of function (LOF) variants, including nonsense, frameshift, and splice acceptor loss (Hughes et al. 2020. PubMed ID: 31883643). To date, copy number variant alterations of PPP1R12A have not been associated with GUBS.

In gnomAD, PPP1R12A is predicted to tolerate missense variants, but has very low tolerance for LOF variants. The most common LOF variant in gnomAD is c.1823+2T>C, which has a minor allele frequency of 0.009%. The pathogenic variants reported by Hughes and colleagues (Hughes et al. 2020. PubMed ID: 31883643) are not present in gnomAD.

Several animal models including mouse, C. elegans, and Drosophila have been generated that demonstrate a role for the homologues of PPP1R12A in embryonic development (Okamoto et al. 2005. PubMed ID: 16145842; Wissmann et al. 1999. PubMed ID: 10208747; Mizuno et al. 2002. PubMed ID: 11874917; Tan et al. 2003. PubMed ID: 12505998). Of note, a zebrafish model was shown to have malformations consistent with phenotypes observed in humans with holoprosencephaly (Weiser et al. 2009. PubMed ID: 19515695). PPP1R12A has been cited as an essential gene under certain conditions--meaning that some cell lines require PPP1R12A for proliferation, whereas others do not (Online Gene Essentiality, ogee.medgenius.info).

PPP1R12A encodes a subunit of the myosin phosphatase protein which is a key enzyme for regulating cell motility and morphology (Kiss et al. 2019. PubMed ID: 30076859). For example, the subunit encoded by PPP1R12A is essential for smooth muscle contraction (Qiao et al. 2014. PubMed ID: 24951589).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test is difficult to estimate based on the phenotypic overlap with other disorders featuring developmental delay, brain malformations, and/or genitourinary malformations. Other disorders with similar clinical features include Smith-Lemli-Opitz syndrome, X-linked lissencephaly, orofacial digital syndrome IV, pontocerebellar hypoplasia type 7, and other conditions featuring brain and genitourinary anomalies. Analytical sensitivity should be high.

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 PPP1R12A 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

Candidates for this test include individuals with a family history of GUBS and/or the presence of phenotypes such as developmental delay, brain malformations, or genitourinary anomalies. Targeted testing is indicated for family members of patients who have a known pathogenic variant in PPP1R12A.

Gene

Official Gene Symbol OMIM ID
PPP1R12A 602021
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Genitourinary and/or/brain malformation syndrome AD 618820

Citations

  • Hughes et al. 2020. PubMed ID: 31883643
  • Kiss et al. 2019. PubMed ID: 30076859
  • Mizuno et al. 2002. PubMed ID: 11874917
  • Okamoto et al. 2005. PubMed ID: 16145842
  • Online Gene Essentiality (OGEE).
  • Qiao et al. 2014. PubMed ID: 24951589
  • Tan et al. 2003. PubMed ID: 12505998
  • Weiser et al. 2009. PubMed ID: 19515695
  • Wissmann et al. 1999. PubMed ID: 10208747

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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