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Centre for Amyloidosis and Acute Phase Proteins

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Molecular Genetic Testing

The NAC is the world's largest and only centre in the UK specialising in diagnosis, research and management of amyloidosis and hereditary systemic autoinflammatory diseases (SAIDs).

The Jack O’Neill Laboratory of Amyloidosis Research and Diagnosis at the NAC provides a comprehensive molecular diagnostic service for hereditary amyloidosis and SAIDs.  Our SAIDs and hereditary amyloidosis next generation sequencing (NGS) gene panels consist of up to date clinically relevant genes, as determined by our highly specialised clinical consultants.

The testing our laboratory performs is listed in the 2020/2021 National Genomic Test Directory:  

  • For hereditary systemic amyloidosis the clinical indications ID is R204
  • For autoinflammatory syndromes (previously described as fever syndromes)  the clinical indications ID is R15 (this is currently listed in the Primary immunodeficiency)
Key staff
Head of ServiceDorota Rowczenio PhD FRCPathdorota.rowczenio@nhs.net
Quality ManagerHadija Trojerhadija.trojer@nhs.net
Genetics/Pathology SecretaryMelanie Fullermelanie.fuller@nhs.net

For carrier, predictive testing or screening of a single gene we recommend the Sanger sequencing method.  For testing of a wider range of genes, in particular for patients with suspected SAIDs, we recommend our NGS gene panel.  The NGS libraries are prepared using the TruSeq Custom Amplicon method and sequenced on the Illumina MiSeq platformThe sensitivity of our SAIDs panel is sufficient to detect somatic variants (<10% of the minor allele frequency). We have lately identified numerous patients with late onset SAIDs due to acquired mutations.

In order for our genetics team to process the sample, please register and complete the on-line questionnaire using the link provided below.  Our web link contains all the information needed to complete the application form prior to genetic testing.

Charges for your genetic testing may occur.  Unless exempt, the following fees will be implemented: £150 for carrier and predictive testing of known mutations, £400 for screening of a single gene using the Sanger sequencing method; £700 for NGS gene panels for hereditary amyloidosis or SAIDs. You will be requested to provide a purchase order number. Please contact the pathology secretary for more information Melanie Fuller.

For any technical questions regarding the DNA testing please contact Dr Dorota Rowczenio tel  +44 (0)20 7433 2760.

 

Information for Users including Sample Transportation

The Jack O'Neill Amyloidosis Laboratory is open from 9am - 5 pm Mnday to Friday.

Reception desk is open from 9am - 5 pm Monday to Friday.

For sample shipment, we recommend you to use special delivery during weekdays to avoid sample deterioration.

All samples must be sent to the following address:

 

SPECIMEN RECEPTION
National Amyloidosis Centre
Division of Medicine
University College London Medical School
Royal Free Campus
Rowland Hill Street
London NW3 2PF

 

Sample requirement:

  • 2-5 ml whole EDTA blood or a minimum of 50µL DNA sample.

Sample Rejection Criteria:

  • If the details on the sample do not match those on the request form or the sample is unlabelled it will be rejected.

Sample Acceptance Criteria:

  • Sample must be clearly labelled with patient’s full name and date of birth.
  • All samples must be accompanied by clinical information i.e completed electronic questionnaire (see below, Sequencing Request section) 

Genetic Testing Limitation:

  • Inadequate or poor sample quality may not be sufficient for the laboratory to perform the test in such a case we will contact the referring laboratory to provide a new sample

Requesting a test

To request molecular genetic screening the physician should follow the steps below.  Before requesting a genetic test please ensure either EDTA blood or DNA sample is clearly labelled with full name and date of birth.

Step 1:  Select the following site where you will be asked to register or login:

Sequencing Request

Step 2:  Enter the patient’s details and select and complete one of two questionnaires (hereditary fever syndromes or amyloidosis) indicating if a single gene testing or the gene panel analysis should be applied when processing the sample.

Step 3: Once the questionnaire is completed, you will see instructions for specimen collection and posting. Please print the Patient Request Form and post together with the bloods/DNA to Specimen Reception at the National Amyloidosis Centre.  You will receive an email acknowledging receipt of the samples.  A report will be posted to you when tests are completed and checked, generally in 4-6 weeks for Sanger sequencing, and up to 12 weeks for the next generation gene panel request.

If you encounter any problems accessing this site please contact the Genetics Secretary, Melanie Fuller, tel +44 (0)20 7433 2830; fax +44 (0)20 7433 2817.

Predictive genetic testing and clinical advice

Any clinical advice, also including predictive genetic testing in asymptomatic individuals (for example, family screening), must be discussed with one of our consultant staff. 

Please contact Professor Philip Hawkins or Professsor Helen Lachmann.

Requests for test results

Our turnaround time is 4-6 weeks for Sanger sequencing and up to 12 weeks for for the next generation gene panel request. In case of an urgent test please contact the head of the Genetic Lab (Dorota Rowczenio) or the Genetics Secretary (Melanie Fuller). Please check with your Pathology or Genetics Laboratory for copies of reports before contacting the National Amyloidosis Centre as all reports are copied to the appropriate laboratory, where details have been provided, at the time of issue. Please contact our Genetic Secretary if you have not received a genetic report.

Please note, it is our policy not to issue verbal results.  Reports are either sent by Royal Mail or can be emailed only to the confidential nhs.net account to the referring clinician/laboratory.  Requests for copies of reports on the day that your patient is in clinic cannot normally be accommodated; we usually require at least 24 hours notice.

Protection of Personal information:

All laboratory staff complete UCL and Royal Free London NHS Foundation Trust ,mandatory training in the following topics:

  • Information Security
  • GDPR
  • Fraud and Security
  • Information Governance

Quality assurance

As part of its commitment to quality, the National Amyloidosis laboratory participates annually in the external quality assurance schemes for Systemic Autoinflammatory Diseases, DNA sequencing NGS run by the European Molecular Genetics Quality Network (EMQN).  Copies of the results of these external quality assessments are available on request.  Currently there is no equivalent scheme for hereditary amyloidosis.

Please help us improve the service and direct compliments and complaints in writing to the Quality Manager, Hadija Trojer.

See the National Amyloidosis Centre Overview for more in depth information on our services and The Registry of Hereditary Auto-inflammatory Disorders Mutations for information on hereditary fever genetics or The Registry for Mutations and Phenotypes in Hereditary Amyloidosis for information on hereditary amyloidosis genes.

List of genes in the Autoinflammatory and Amyloid Panel

Gene NameGene SymbolChromosomal Location
caspase recruitment domain family member 14CARD1417q25.3
adenosine deaminaseADA2, previous gene symbol CECR122q11.1
interleukin 1 receptor antagonistIL1RN2q14.1
interleukin 36 receptor antagonistIL36RN2q14.1
lipin 2LPIN218p11.31
MEFV, pyrin innate immunity regulatorMEFV16p13.3
mevalonate kinaseMVK12q24.11
NLR family CARD domain containing 4NLRC42p22.3
NLR family pyrin domain containing 12NLRP1219q13.42
NLR family pyrin domain containing 3NLRP31q44
nucleotide binding oligomerization domain containing 2NOD216q12.1
OTU deubiquitinase with linear linkage specificityOTULIN5p15.2
phospholipase C gamma 2PLCG216q24.1
proteasome subunit beta 8PSMB86p21.32
proteasome subunit beta 4PSMB41q21.3
proteasome subunit beta 9PSMB96p21.32
proline-serine-threonine phosphatase interacting protein 1PSTPIP115q24.3
RANBP2-type and C3HC4-type zinc finger containing 1RBCK120p13
SH3 domain binding protein 2SH3BP24p16.3
solute carrier family 29 member 3SLC29A312p13.31
TNF alpha induced protein 3TNFAIP36q23.3
TNF receptor superfamily member 1ATNFRSF1A10q22.1
transmembrane protein 173TMEM1735q31.2
ubiquitin like modifier activating enzyme 1UBA1Xp11.3

List of Genes in the Hereditary Amyloidosis NGS Panel

Gene NameGene SymbolChromosomal Location
Amyloid P component, serumAPCS, synonym SAP1q23.2
Apolipoprotein EAPOE19q13.32
Apolipoprotein A4APOA411q23.3
Apolipoprotein A1APOA111q23.3
Apolipoprotein A2APOA21q23.3
Apolipoprotein C2APOC219q13.32
Apolipoprotein C3APOC311q23.3
Serum amyloid A1SAA111p15.1
Serum amyloid A2SAA211p15.1
Serum amyloid A4SAA411p15.1
C-reactive proteinCRP1q23.2
LysozymeLYZ12q15
GelsolinGSN9q33.2
fibrinogen alpha chainFGA4q31.3
beta-2-microglobulinB2M15q21.1
transthyretinTTR18q12.1
Cystatin CCST320p11.21
leukocyte cell derived chemotaxin 2LECT25q31.1
myeloid differentiation primary response 88MYD883p22.2
transforming growth factor beta inducedTGFBI, synonym BIGH35q31.1
Oncostatin M ReceptorOSMR5p13.1
Galectin 7LGAL5719q13.2