Aminoglycosides are a large class of antibiotics widely used around the world for the treatment of infection. They include gentamicin, amikacin, tobramycin, streptomycin and neomycin. Aminoglycosides are typically administered by intravenous or intramuscular injection for the treatment of gram-negative bacterial infections, or as synergistic treatment for gram-positive bacterial infections.

GeNotes has produced a helpful summary about Aminoglycosides and MT-RNR1 testing: Aminoglycoside antibiotics — Knowledge Hub

MT-RNR1 is a gene found in the DNA of our mitochondria. We inherit all of our mitochondria from our mother. This means that we inherit our MT-RNR1 gene from our mother. We can not inherit it from our father.

Some people have a variant in the MT-RNR1 gene that predisposes them to ototoxicity after just a single dose of aminoglycoside. These people may experience Aminoglycoside-induced hearing loss following exposure to the drug.

Genetic testing is now available to detect some variants in the MT-RNR1 gene. This test can be used to identify individuals at risk of developing Aminoglycoside-induced hearing loss.

Patients can be offered MT-RNR1  testing if they are likely to experience significant exposure to aminoglycosides posing risk of ototoxicity, or if they have hearing loss and have previously been exposed to aminoglycosides

This indication would be relevant to:
1. individuals with a predisposition to gram negative infections for example due to known respiratory
disease (e.g. bronchiectasis, cystic fibrosis) or due to structural or voiding genitourinary tract disorders,
OR
2. individuals with hearing loss who have been exposed to aminoglycosides*

Referrals for testing will be triaged by the Genomic Laboratory; testing should be targeted at those where a
genetic or genomic diagnosis will guide management for the proband or family.

*The genomic test ‘R67 Monogenic hearing loss’ should be used in individuals with unexplained hearing loss More information about R67

A standard CF carrier test looks for the 50 most common CF gene variants that account for 90% of CF diagnoses in northern European population. This mean that whilst a ‘normal’ result is reassuring, the test cannot exclude the possibility that someone carries a rare CF variant that would not be detected by the test.

If your patient’s relative has been found to have a rare CF variant, the scientists can also test your patient for this variant. This is why it is important to include details of affected family members in the ‘clinical information and family history’ box on the Test Order Form; it allows the laboratory to link family members.

Before arranging testing, you should explain the possible outcomes of the test to your patient. You can use the Record of Discussion (RoD) form to help with this.

You then need to complete a Test Order Form and obtain a blood sample in an EDTA tube (purple top)

The Test Order Form and blood sample should be sent to:

Genetics Laboratory
5th Floor Tower Wing
Guy’s Hospital
London
SE1 9RT

Download copies of the Record of Discussion Form and Test Order Form here

You can download copies of the Test Order Form from the Cystic fibrosis carrier testing page.

The Record of Discussion form can be used to explain to the patient what the potential outcomes of the test could be.

You can download copies of the Record of Discussion Form from the Cystic fibrosis carrier testing page.

A standard CF carrier test looks for the 50 most common CF gene variants that account for 90% of CF diagnoses in northern European population. If your patient does not have northern European ancestry, there may be a greater chance that they carry a gene variant that will not be detected by the test. When you include your patient’s ethnicity on the form, this helps the scientists to predict the chances of your patient being a carrier if they receive a ‘normal’ result.

The sample should be collected in an EDTA tube (purple top)

Please include as much detail as possible in this box, including the reason for offering the patient a test.

If the patient is having testing because their partner is a carrier of CF, please include the partner’s name, DOB and NHS number if possible. This allows the lab to combine the couple’s results and predict the chances of them having an affected child.

If the patient is having testing because their relative has CF, please include details of the affected relative (name and DoB) and your patient’s relationship to the relative e.g. brother, first cousin.

A test should only be requested urgently if there is a clinical need to do so. For example, if the patient is pregnant.

If a couple is pregnant, urgent carrier testing will need to be arranged for both parents at the same time (if neither have been tested previously). You will need to tick the urgent box and indicate that they are pregnant on the test request form. If they are both found to be carriers, they should be urgently referred to Clinical Genetics to discuss their options, including the possibility of arranging testing to determine if the pregnancy has inherited CF.

Pregnant couples who are both found to be carriers of CF should be referred to Clinical Genetics even if they do not wish to pursue any further genetic testing during pregnancy. This is because the Clinical Genetics team can liaise with the Midwife and Neonatal teams to ensure that an appropriate care plan is in place for when the baby is born.

The code for CF carrier testing is ‘R185 Cystic fibrosis carrier testing’. Please write this on the test request form.

Please write your name and contact details in this box. As the requesting clinician, you will receive the report and it is your responsibility to inform the patient of the result.

A test should only be requested urgently if there is a clinical need to do so. For example, if the patient is pregnant.

If a couple is pregnant, urgent carrier testing will need to be arranged for both parents at the same time (if neither have been tested previously). You will need to tick the urgent box and indicate that they are pregnant on the test request form. If they are both found to be carriers, they should be urgently referred to Clinical Genetics to discuss their options, including the possibility of arranging testing to determine if the pregnancy has inherited CF.

Pregnant couples who are both found to be carriers of CF should be referred to Clinical Genetics even if they do not wish to pursue any further genetic testing during pregnancy. This is because the Clinical Genetics team can liaise with the Midwife and Neonatal teams to ensure that an appropriate care plan is in place for when the baby is born.

Being a carrier of CF is not associated with any health problems. If your patient is a carrier, then please encourage them to share this information with family members so they can be tested via their GP. It would be appropriate to arrange genetic testing for their partner, if applicable.

If people in a couple are both carriers for CF, there is a 1 in 4 (25%) chance that they could have a child affected by CF. Couples who are both carriers of CF can be referred to Clinical Genetics to discuss their reproductive options.

GeNotes has produced a helpful summary about Cystic Fibrosis:  GeNotes Cystic fibrosis

The Clinical Genetics team at Guys and St Thomas’s NHS Foundation Trust have produced a patient leaflet explaining CF carrier testing.

Download Patient Leaflet

Your patient may also find it helpful to visit the website of the Cystic Fibrosis Trust to access more information about the condition and the support available: Cystic Fibrosis Trust

The Clinical Genetics team at Guys and St Thomas’s NHS Foundation Trust have produced a patient leaflet explaining CF carrier testing.

Download Patient Leaflet

If you can not find the answer to your question on this page, you can contact your local Clinical Genetics service for support.

• Clinical Genetics at Guy’s and St Thomas’s NHS Foundation Trust: gstt.geneticscorrespondence@nhs.net
• Clinical Genetics at St George’s University Hospitals NHS Foundation Trust: genetic.secretaries@stgeorges.nhs.uk