At this time, participants must be referred to UDN-Aus via a participating Clinical Genetics Service. If you are a Clinical Geneticist you can discuss the eligibility of your patient with the Principal Investigator or Associate Investigator for your state or service. Find your state lead Principal Investigator here.

If you are another Health Professional and suspect your patient may have an undiagnosed genetic disease, please refer them to their local Clinical Genetics Service for investigation. A directory of Clinical Genetics Services across Australasia can be found here. Select Health Professional Resources, Clinical Genetics Services from the menu options and view by state/territory.

Please note that Clinical Genetics Services may have specific referral criteria for which you should visit their respective websites.

This criteria is aimed at Clinical Geneticists and contains technical/jargon language. If you are unsure if you meet this criteria or would like any aspect clarified, contact your Genetics Service (or see the FAQ For Families “What if I don’t have a Clinical Geneticist?”.

Developed in consultation with our Community Advisory Committee, this criteria will be iteratively reviewed over the course of the study, so we can learn key lessons from this process and adapt if required.

Inclusion criteria

1. Patient has a high likelihood of a monogenic cause for their condition but remains without a confirmed genetic diagnosis despite clinically indicated appropriate diagnostic testing.  (See prioritisation criteria Categories A and B below.)

   For most phenotypes, appropriate diagnostic testing means a non-diagnostic genomic test (most commonly exome sequencing), but may also mean, depending on phenotype, additional tests such as chromosomal microarray, expansion testing, methylation etc.

   N.B. first-line tests should have been completed at the state/territory level prior to consideration by UDN-Aus 

2. Any age

3. Lives in Australia

4. Is referred to their study from a clinical genetics service

5. Genomic data available for transfer into the UDN-Aus bioinformatics system readily

6. Potential for a diagnosis to impact care of the patient and family i.e. likelihood that a genetic diagnosis would change management, impact reproductive counselling, improve psychosocial/mental health outcomes for family etc. (i.e. treatment options, reproductive decision-making, clinical surveillance)

Exclusion criteria

1. Low likelihood monogenic condition

2. Clinically indicated first-line tests not yet done at state/territory level

3. Proband does not live in Australia

4. Genomic data is stored in a laboratory where it cannot be transferred into the UDN-Aus bioinformatics system readily.

   N.B. Data sharing agreements or processes are being sought/ have been approved with the following laboratories: VCGS (VIC), NSW Health Pathology, Pathology Queensland, SA Pathology and PathWest (WA).

5. No availability of samples e.g., no clinically accessible tissue appropriate for study

6. Low potential for a diagnosis to impact care of the patient and family i.e., low likelihood that a genetic diagnosis would change management, impact reproductive counselling, improve psychosocial/mental health outcomes for family etc.

   It is important to avoid unduly raising expectations.

Prioritisation criteria

One point will be assigned for each of the below criteria if met

A: High likelihood of finding an answer through UDN-Aus with resources available and timeline of project

1. Multi-systems involved (may need to consider single systems on case-by-case basis) *

2. Severe intellectual disability (ID) OR ID of any level + other features (e.g., dysmorphism, epilepsy, movement disorder) - do not double count with Criterion 1

3. Identifiable specific phenotype with no definitive molecular diagnosis identified after appropriate testing, including two or more individuals with a similar phenotype (cohort)**

4. Single variant in a gene associated with AR disease that fits phenotype of patient ***

B: Optional criteria for consideration by Clinical Review Committee if criteria from Category A are equivocal.

1. In the presence of a family history, phenotype segregates with Mendelian inheritance

2. Consanguineous **** parents (don’t count if B1 selected)

3. De novo VUS/GUS

4. Phenotype that has high likelihood of discovery of novel gene

5. Phenotype that has high likelihood of discovery of novel mechanism

* Single system phenotypes might be lower priority than multisystem disorders, due to the clinical utility of testing

** If you have a cohort of patients you would like to enrol in this study, please discuss this with your state clinical lead

*** Variants of unknown significance (VUS) in a gene with potential to discover a novel mechanism of disease e.g., non-nonsense mediated decay (NMD)-predicted VUS associated with phenotype that is atypical or different to phenotype associated with loss of function (LOF) variants: should be prioritised to the Australian Functional Genomics Network (AFGN)

****Especially if limited regions of loss of heterozygosity (LOH)

C: Equity

1. Individuals living in regional and remote centres*

2. Aboriginal and Torres Strait Islander individuals

3. Individuals of culturally and linguistically diverse backgrounds

4. Individuals with low socioeconomic status**

5. Individuals who identify as gender diverse

6. Individuals with disability (other than neurodevelopmental disability if counted under criteria A)

7. Individuals undiagnosed for more than 2 years

8. No alternative diagnostic pathways available***

*Those classified as living in zone 3 and above using the Rural, Remote and Metropolitan Area classification map

** as per proxy measure e.g. postcode classified in the lowest 25% of the Australian Bureau of Statistics' Socio Economic Indexes for Areas and/or family accessing income support

*** e.g. other MRFF funded undiagnosed disease programs such as mitoMDT or KidGEN