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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).

Key staff

Head of Service

Dorota Rowczenio PhD FRCPath

dorota.rowczenio@nhs.net

Quality Manager

Hadija Trojer

hadija.trojer@nhs.net

Genetics/Pathology Secretary

Melanie Fuller

melanie.fuller@nhs.net

The Jack O’Neill Laboratory of Amyloidosis Research and Diagnosis at the NAC provides a comprehensive molecular diagnostic service for hereditary amyloidosis and systemic autoinflammatory syndromes (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)

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 sequenced on the Illumina MiSeq platform.  The sensitivity of both panels is sufficient to detect somatic variants (<10% of the minor allele frequency). This has enabled us to identify acquired mutations, in particular in patients with SAIDs.

Information for Users:

Sample Transportation

The Jack O'Neill Amyloidosis Laboratory is open from 9am - 5 pm Monday 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 unlabeled 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 genetic test

In order for our genetic team to process the sample, please register and complete the on-line request form using the link provided below. If you encounter any problems accessing this site please contact the Genetic Secretary, Melanie Fuller, Tel +44 (0)20 7433 2830.

We ask you to provide patient's clinical symptoms. This information is vital while making decisions on genotype-phenotype correlations.

Sequencing Request

Step 1:  Click on the Sequencing Request button, you will be asked to register or login:

Step 2:  Enter the patient’s details and select and complete one of two questionnaires (SAIDs or hereditary 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 test is completed; generally in 4-6 weeks for Sanger sequencing, and up to 12 weeks for NGS gene panel request.

In case of an urgent test please contact the Head of the Genetics Lab Dorota Rowczenio

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 Melanie Fuller 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 to the referring clinician/laboratory confidential nhs.net account.  Requests for copies of reports on the day that your patient is in clinic cannot normally be accommodated; we usually require at least 24 hour notice.

Charges for genetic request may occur (outside of England).  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 genetic/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.

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 Helen Lachmann.

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 Name

Gene Symbol

Chromosomal Location

caspase recruitment domain family member 14

CARD14

17q25.3

adenosine deaminase

ADA2, previous gene symbol CECR1

22q11.1

interleukin 1 receptor antagonist

IL1RN

2q14.1

interleukin 36 receptor antagonist

IL36RN

2q14.1

lipin 2

LPIN2

18p11.31

MEFV, pyrin innate immunity regulator

MEFV

16p13.3

mevalonate kinase

MVK

12q24.11

NLR family CARD domain containing 4

NLRC4

2p22.3

NLR family pyrin domain containing 12

NLRP12

19q13.42

NLR family pyrin domain containing 3

NLRP3

1q44

nucleotide binding oligomerization domain containing 2

NOD2

16q12.1

OTU deubiquitinase with linear linkage specificity

OTULIN

5p15.2

phospholipase C gamma 2

PLCG2

16q24.1

proteasome subunit beta 8

PSMB8

6p21.32

proteasome subunit beta 4

PSMB4

1q21.3

proteasome subunit beta 9

PSMB9

6p21.32

proline-serine-threonine phosphatase interacting protein 1

PSTPIP1

15q24.3

RANBP2-type and C3HC4-type zinc finger containing 1

RBCK1

20p13

SH3 domain binding protein 2

SH3BP2

4p16.3

solute carrier family 29 member 3

SLC29A3

12p13.31

TNF alpha induced protein 3

TNFAIP3

6q23.3

TNF receptor superfamily member 1A

TNFRSF1A

10q22.1

transmembrane protein 173

TMEM173

5q31.2

ubiquitin like modifier activating enzyme 1

UBA1

Xp11.3

List of Genes in the Hereditary Amyloidosis NGS Panel

Gene Name

Gene Symbol

Chromosomal Location

Amyloid P component, serum

APCS, synonym SAP

1q23.2

Apolipoprotein E

APOE

19q13.32

Apolipoprotein A4

APOA4

11q23.3

Apolipoprotein A1

APOA1

11q23.3

Apolipoprotein A2

APOA2

1q23.3

Apolipoprotein C2

APOC2

19q13.32

Apolipoprotein C3

APOC3

11q23.3

Serum amyloid A1

SAA1

11p15.1

Serum amyloid A2

SAA2

11p15.1

Serum amyloid A4

SAA4

11p15.1

C-reactive protein

CRP

1q23.2

Lysozyme

LYZ

12q15

Gelsolin

GSN

9q33.2

fibrinogen alpha chain

FGA

4q31.3

beta-2-microglobulin

B2M

15q21.1

transthyretin

TTR

18q12.1

Cystatin C

CST3

20p11.21

leukocyte cell derived chemotaxin 2

LECT2

5q31.1

myeloid differentiation primary response 88

MYD88

3p22.2

transforming growth factor beta induced

TGFBI, synonym BIGH3

5q31.1

Oncostatin M Receptor

OSMR

5p13.1

Galectin 7

LGAL57

19q13.2