Maternally inherited diabetes and deafness

The mitochondrial variant m.3243A>G is associated with the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes; Goto et al 1990 Nature 348: 651-653) and the MIDD syndrome (maternally inherited diabetes and deafness; Ballinger et al 1992 Nat Genet 1: 11-15). Additional clinical features associated with the m.3243A>G variant include short stature, cardiomyopathy, myopathy, renal disease, macular dystrophy and gastrointestinal disease (Murphy et al 2008 Diabet Med 25: 383-399). Mitochondrial variants are passed on through the maternal germline, and so all maternal relatives of an individual with MIDD or MELAS are likely to be obligate carriers of the m.3243A>G variant. However the clinical phenotype associated with the m.3243A>G variant may be very heterogeneous, even within the same family s (Nesbitt et al 2013 J Neurol Neurosurg Psychiatry 84: 936-938). Part of this variation in phenotype is due to the amount of heteroplasmy (the mixture of wild-type and mutant mitochondrial DNA in each cell) inherited, the subsequent segregation of mutant mitochondrial DNA in the different tissues and changes in the level of heteroplasmy in different tissues with increasing age.

Mitochondrial variant m.3243A>G in melas or diabetes and deafness.

Visit the NHS Genomic Test Directory 

Eligibility criteria for genomic tests can be found in the National Genomic Test Directory.

This lists the clinical specialties that would be expected to request for a given clinical indication and sets out which patients should be considered for testing.

All samples for genomic testing should be accompanied by a fully completed request form.

The request form should include as much clinical information about the patient or family member, family relationships and the requested test code (R number). All request forms must indicate either a specific disorder/gene(s) to be investigated or, a request to extract and store DNA. This form should be used for the majority of test requests.

Please do not download and store this on your desktop or system. The form is regularly updated. Our recommendation is to save or bookmark a link to our website to ensure you are working with the most up-do-date version.

Download the form here

An appropriate discussion of genomic testing and the possible implications for a patient and their family members must take place before testing is requested.

It is the referring clinician’s responsibility to ensure that the patient/carer knows the purpose of the test and that the sample may be stored for future diagnostic testing. In submitting a sample with a request form, the clinician confirms that informed consent has been obtained for (a) testing and storage (indefinitely) (b) the use of this sample and the information generated from it to be shared with members of the donor’s family and their health professionals (if appropriate). The patient should be advised that the samples may be used anonymously for quality assurance and training purposes.

If stated as a requirement for a specific test, a record of this discussion must be retained within the patient record when a genomic test is ordered.

For more information please view the Consent and Confidentiality in Genomic Medicine guidelines from the Joint Committee on Medical Genetics.

Before sending samples for genomic testing, please ensure you follow the correct preparation and transport guidelines. This includes information on sample types, volumes, handling, labelling, and packaging standards.

The m.3243A>G mutation can be detected in virtually all tissues; however heteroplasmy differs between sample types. Blood leukocytes generally contain the lowest level of the m.3243A>G mutation. Therefore it is possible to obtain a negative result for m.3243A>G in blood, despite the presence of the mutation in other tissues. Of the readily accessible tissues available for testing, urine epithelial cells contain the highest level of the m.3243A>G mutation and urine is therefore the preferred sample to test (de Laat et al 2012 J Inherit Metab Dis 35: 1059-1069) Urine: Collect the first 20ml of an early morning urine sample into a sterile universal container. Send to the laboratory with a completed request form by first class post on the day the sample is taken Blood: Please send at least two 4ml EDTA blood samples (1ml minimum for neonates, 5-10ml for children and 10-20ml for adults). Samples should be transported at ambient temperature. Blood samples in glass bottles are not accepted by the laboratory. Blood samples should be received by our laboratory within 5 days of venesection. Do not freeze blood samples – if storage is required prior to dispatch, blood samples can be stored at 4ºC (39.2ºF). DNA: Please send a minimum of 5μg of DNA. DNA samples can be sent at room temperature. Other: In special circumstances, a saliva sample is acceptable. Please contact the laboratory for sample collection kits and/or instructions for collection (Oragene). Please contact the laboratory prior to sending any other samples (e.g. paraffin-embedded tissue sections).

For a full list of sample requirements and transport guidance, please visit the samples and transport page of the website. 

Turnaround times (TATs) for genomic tests are continually refined through ongoing reviews of testing standards.

Results will be returned to the email account or clinician listed on the request form.

Visit the results and turnaround page for more information.