Comprehensive Brain Malformation Panel - Clinical Genetic Test - GTR

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Comprehensive Brain Malformation Panel

Clinical Genetic Test

offered by

Genetic Services Laboratory

View lab's test page

GTR Test Accession: GTR000500161.5

CAP

INHERITED DISEASENERVOUS SYSTEMDYSMORPHOLOGY ... View more

Last updated in GTR: 2021-01-20

Last annual review date for the lab: 2024-07-22

At a Glance

Test purpose:

Diagnosis; Monitoring; Mutation Confirmation; ...

Conditions (37):

Lissencephaly; Bilateral frontoparietal polymicrogyria; CEDNIK syndrome more...

Genes (131):

ACTB (7p22.1); ACTG1 (17q25.3); ADGRG1 (16q21); AIMP1 (4q24); AKT3 (1q43-44) more...

Methods (2):

Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...

Target population:

Not provided

Clinical validity:

The genetic causes of lissencephaly are complex LIS1 [OMIM#601545] abnormalities …

Clinical utility:

Not provided

Ordering Information

Offered by:

Genetic Services Laboratory
View lab's website
View lab's test page

Specimen Source:

Amniocytes
Amniotic fluid
Buccal swab
Cell culture
Chorionic villi
Cord blood
Fetal blood
Fibroblasts
Fresh tissue
Frozen tissue
Peripheral (whole) blood
Product of conception (POC)
Saliva
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner
Physician Assistant
Registered Nurse

Test Order Code:

1130
View other test codes

CPT codes:

81443

**AMA CPT codes notice

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

All samples should be shipped via overnight delivery at room temperature.
No weekend or holiday deliveries.
Label each specimen with the patient’s name, date of birth and date sample collected.
Send specimens with complete requisition and consent form, otherwise, specimen processing may be delayed.
Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings

Test additional service:

Custom Prenatal Testing
Custom mutation-specific/Carrier testing

Test development:

Test developed by laboratory but exempt from FDA oversight (eg. NYS CLEP approved, offered within a hospital or clinic)

Informed consent required:

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Recommended fields not provided:

Lab contact for this test, Test strategy

Conditions

Total conditions: 37

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 131

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

Instrument *

Deletion/duplication analysis

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

* Instrument: Not provided

Clinical Information

Test purpose:

Diagnosis; Monitoring; Mutation Confirmation; Pre-symptomatic; Risk Assessment; Screening

Clinical validity:

The genetic causes of lissencephaly are complex LIS1 [OMIM#601545] abnormalities cause the most severe form of lissencephaly and are generally associated with a p>a gradient. LIS1 mutations are present in approximately 30% of patients with LIS1-related lissencephaly and rarely in patients with SBH. Microdeletions involving 17p13.3 are present in 100% … The genetic causes of lissencephaly are complex LIS1 [OMIM#601545] abnormalities cause the most severe form of lissencephaly and are generally associated with a p>a gradient. LIS1 mutations are present in approximately 30% of patients with LIS1-related lissencephaly and rarely in patients with SBH. Microdeletions involving 17p13.3 are present in 100% of patients with MDS and approximately 50% of patients with lissencephaly. Intragenic deletions of one or more exons of LIS1 are present in approximately 15% of patients with LIS1-related lissencephaly. DCX [OMIM#300121] abnormalities result in severe lissencephaly or SBH in boys, but a less severe SBH in girls. DCX abnormalities are generally associated with an a>p gradient. In males, DCX mutations are present in approximately 30% with SBH and approximately 10% with lissencephaly. In females, DCX mutations are present in approximately 80% with SBH, especially those with diffuse bands or bilateral frontal only bands. Intragenic deletions of the DCX gene are present in approximately 10% of female patients with SBH in whom no mutations were identified by DCX sequencing. TUBA1A [OMIM#602529] mutations have been identified in patients with gyral malformations and are generally associated with a p>a gradient (similar to LIS1-associated lissencephaly). Of patients with cortical dysgeneses in whom DCX, LIS1, and ARX mutation analysis is normal, approximately 30-40% have mutations in the TUBA1A gene. ARX [OMIM#300382] mutations cause various phenotypes including XLAG, X-linked infantile spasms, and non-syndromic X-linked mental retardation. RELN mutations have been identified in patients with a less severe form of lissencephaly with cerebellar hypoplasia (LCH). VLDLR-associated cerebellar hypoplasia (VLDLR-CH) falls within the LCH spectrum, and is characterized by non-progressive congenital ataxia, ID, dysarthria, strabismus and seizures. These patients have mild lissencephaly as well. VLDR is part of the reelin (RELN) signaling pathway, which guides neuroblast migration in the cerebral cortex and cerebellum. LCH is distinguished from VLDLR-CH by more severe lissencephaly with an a>p gradient, a small and malformed hippocampus, and profound cerebellar hypoplasia with complete absence of detectable folia. Baraitser-Winter syndrome is a developmental disorder characterized by congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata and anterior-predominant lissencephaly. Other features include postnatal short stature, microcephaly, ID, seizures and hearing loss . Mutations in both ACTB and ACTG1, which code for cytoplasmic actin, have been identified in patients with Baraitser-Winter syndrome View more

View citations (1)

Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome. Lo Nigro C, et al. Hum Mol Genet. 1997;6(2):157-64. doi:10.1093/hmg/6.2.157. PMID: 9063735.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
Variants are identified and evaluated using a custom collection of bioinformatic tools and comprehensively interpreted by our team of directors and genetic counselors.

Will the lab re-contact the ordering physician if variant interpretation changes?
Yes.

Research:

Is research allowed on the sample after clinical testing is complete?
http://dnatesting.uchicago.edu/research-consent-form

Recommended fields not provided:

Clinical utility, Target population, Are family members with defined clinical status recruited to assess significance of VUS without charge?, Sample negative report, Sample positive report

Technical Information

Test Procedure:

Positive test results are confirmed using repeat analysis.

Test Confirmation:

Positive test results are confirmed using repeat analysis.

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

Analytical Sensitivity 99-100% Accuracy 100% Precision 100%

Assay limitations:

This assay covers the coding and immediate flanking regions of the included genes. Variants in the promoter region and in other non-coding regions will not be detected. Variants that occur within regions of high homology and/or repetitiveness may not be detected due to issues with alignment. The technical sensitivity of … View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Formal PT program

PT Provider:
American College of Medical Genetics / College of American Pathologists, ACMG/CAP

VUS:

Software used to interpret novel variations
A custom collection of bioinformatics tools

Laboratory's policy on reporting novel variations
The laboratory reports novel variations.

Recommended fields not provided:

Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

PubMed Clinical Queries

Clinical resources:

Consumer resources:

NCATS Office of Rare Diseases Research (GARD)

MedlinePlus

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.