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NIPBL mutation analysis
Clinical Genetic Test
Help
offered by
Amsterdam UMC Genome Diagnostics
View lab's test page
LinkOut
GTR Test Accession: Help GTR000244759.7
INHERITED DISEASEDYSMORPHOLOGYMUSCULOSKELETAL ... View more
Last updated in GTR: 2018-11-15
View version history
Last annual review date for the lab: 2024-04-16 LinkOut
At a Glance
Test purpose: Help
Diagnosis; Mutation Confirmation; Pre-symptomatic; ...
Conditions (2): Help
Cornelia de Lange syndrome 1; De Lange syndrome
Genes (1): Help
NIPBL (5p13.2)
Methods (1): Help
Molecular Genetics - Sequence analysis of the entire coding region: Bi-directional Sanger Sequence Analysis
Target population: Help
For patients suspected to this particular disease, NIPBL gene sequence …
Clinical validity: Help
A mutation in this gene is detected in approximately 55% …
Clinical utility: Help
Establish or confirm diagnosis
Ordering Information
Offered by: Help
Amsterdam UMC Genome Diagnostics
View lab's website
View lab's test page
Test short name: Help
NIPBL
Specimen Source: Help
  • Amniocytes
  • Amniotic fluid
  • Buccal swab
  • Cell culture
  • Chorionic villi
  • Cord blood
  • Fetal blood
  • Fibroblasts
  • Fresh tissue
  • Frozen tissue
  • Isolated DNA
  • Peripheral (whole) blood
  • Saliva
  • View specimen requirements
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Physician
  • Physician Assistant
Lab contact: Help
Egbert Redeker, PhD, Staff
KG-DNA@AMC.UVA.NL
+31 205667899
Contact Policy: Help
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: Help
Using our website
Order URL
Test service: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Test additional service: Help
Custom Prenatal Testing
Custom mutation-specific/Carrier testing
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
No
Test strategy: Help
Simultaneous bi-directional sequencing of all coding exons. If the analysis of the NIPBL gene on DNA from lymphocytes detects no mutation, a repeated analysis on DNA of cultured fibroblasts or buccal swabs could be considered.
Pre-test genetic counseling required: Help
Yes
Post-test genetic counseling required: Help
Yes
Recommended fields not provided:
Test Order Code
Conditions Help
Total conditions: 2
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 1
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 1
Method Category Help
Test method Help
Instrument
Sequence analysis of the entire coding region
Bi-directional Sanger Sequence Analysis
Applied Biosystems 3730 capillary sequencing instrument
Clinical Information
Test purpose: Help
Diagnosis; Mutation Confirmation; Pre-symptomatic; Prognostic; Risk Assessment; Screening
Clinical validity: Help
A mutation in this gene is detected in approximately 55% of classical Cornelia de Lange Syndrome patients
Clinical utility: Help
Establish or confirm diagnosis
Target population: Help
For patients suspected to this particular disease, NIPBL gene sequence analysis is recommended as the first step in mutation identification.
View citations (2)
  • Tonkin ET, Wang TJ, Lisgo S, Bamshad MJ, Strachan T. NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome. Nat Genet. 2004;36(6):636-41. doi:10.1038/ng1363. Epub 2004 May 16. PMID: 15146185.
  • Krantz ID, McCallum J, DeScipio C, Kaur M, Gillis LA, Yaeger D, Jukofsky L, Wasserman N, Bottani A, Morris CA, Nowaczyk MJ, Toriello H, Bamshad MJ, Carey JC, Rappaport E, Kawauchi S, Lander AD, Calof AL, Li HH, Devoto M, Jackson LG. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat Genet. 2004;36(6):631-5. doi:10.1038/ng1364. Epub 2004 May 16. PMID: 15146186.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
The 5-classes classification method (Alamut)

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Yes.
Recommended fields not provided:
Are family members with defined clinical status recruited to assess significance of VUS without charge?, Is research allowed on the sample after clinical testing is complete?, Sample negative report, Sample positive report
Technical Information
Test Procedure: Help
DNA is extracted from the patient specimen, PCR amplification and sequence analysis of the entire coding region/ or indicated exons plus additional flanking intronic or other non-coding sequence. Sanger sequencing is carried out and the sequence is visualized on a capillary sequencer. Sequencing is performed separately in both the forward … View more
Test Platform:
None/not applicable
Test Confirmation: Help
Confirmation of identified mutations is done in an independent experiment.
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
This test detects >99% of described mutations. Detection rate of NIPBL mutations in Cornelia de Lange Syndrome patients is approximately 55%, when DNA extracted from EDTA blood is used for mutation analysis. In a number of Cornelia de Lange syndroom patients mutations can only be detected in DNA from fibroblasts … View more
View citations (2)
  • Bhuiyan ZA, Klein M, Hammond P, van Haeringen A, Mannens MM, Van Berckelaer-Onnes I, Hennekam RC. Genotype-phenotype correlations of 39 patients with Cornelia De Lange syndrome: the Dutch experience. J Med Genet. 2006;43(7):568-75. doi:10.1136/jmg.2005.038240. Epub 2005 Oct 19. PMID: 16236812.
  • Huisman SA, Redeker EJ, Maas SM, Mannens MM, Hennekam RC. High rate of mosaicism in individuals with Cornelia de Lange syndrome. J Med Genet. 2013;50(5):339-44. doi:10.1136/jmedgenet-2012-101477. Epub 2013 Mar 15. PMID: 23505322.
Assay limitations: Help
All coding sequences, including the flanking intron sequences are analyzed using direct sequencing. With this method we can detect point mutations and small deletions or insertions. The presence of larger deletions or insertions, or mutations outside the analyzed regions will not be detected.
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
European Molecular Genetics Quality Network, EMQN
VUS:
Software used to interpret novel variations Help
Alamut (Interactive Biosoftware), including AGVGD, PolyPhen-2, SIFT and MutationTaster for missense predictions and MAXEntScan, NNSPLICE, GeneSplicer and Human Splicing Finder for splice predictions

Laboratory's policy on reporting novel variations Help
Our laboratory reports class 3 (unknown pathogenicity), class 4 (likely pathogenic) and class 5 (certainly pathogenic) variants.
Recommended fields not provided:
Citations to support assay limitations, Description of internal test validation method, Description of PT method, Major CAP category, CAP category, CAP test list
Regulatory Approval
FDA Review: Help
Category: Not Applicable
Additional Information

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.