Maclean, Ken --- "Genomics: A new frontier in medical negligence" [2023] PrecedentAULA 5; (2023) 174 Precedent 14

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GENOMICS

A NEW FRONTIER IN MEDICAL NEGLIGENCE

By Dr Ken Maclean

The last two decades have seen an extraordinary advance in DNA sequencing technologies. The immediacy, accuracy and breadth of application of DNA testing to genetic medicine has rapidly established genomics, genetic diagnostics and precision medicine as fundamental pillars of 21st century Australian healthcare. The pace and explosion of scientific discovery and genomic knowledge is, for the judiciary and legal practitioners, creating an urgent challenge as they seek to understand core principles that are clouded by complexity, uncertainty and exceptionalism. Nowhere is this more evident than in wrongful birth and birth injury claims with the increasing use of genomic testing in litigated cases.

Arguably, genomics is forging new standards in the scope of medical negligence, arising from an expansion of duty of care into pre-pregnancy genetic testing; novel clinical scenarios without legal precedent; and the everyday setting of causation, susceptibility and damages. Intermediate courts are yet to deny an application for genetic testing in wrongful birth, birth injury and paediatric claims, irrespective of likelihood, where court orders set aside consent and, potentially, protections for individuals and families from the unintended consequences of DNA testing. It is foreseeable that the scope of duty of care arising from genomic testing, and its role in causation, are likely to come before the higher courts as the judiciary and potentially the executive branch of government seek to determine the limits and limitations of DNA testing in tort law.

GENOMICS – THE NEW GENETICS

The commissioning of the Human Genome Project (HGP) in the United States (US) by President Bush Sr,^[1] and its completion in 2003,^[2] were watershed moments in genetic medicine. The HGP signalled a move away from Mendelian genetics – in which diseases, their clinical classification and prior knowledge of inheritance patterns were central to clinical genetic diagnosis. What is emerging is a new era of clinical genomics.

While the terminology can be used interchangeably, genomics at its core is a collective noun that distinguishes the simplicity of the ‘old’ genetics, which tested a single gene, from the vast complexity of genomic diagnostics, which can test the entirety of the human nuclear and mitochondrial genomes. Examples of single gene disorders are cystic fibrosis, sickle cell disease and Huntington disease. Genomics is a catch-all term for the end-to-end process of sequencing and analysing many if not all genes in a single step.

The nuclear genome has 46 chromosomes encoding ~20,000 genes that are spread somewhat randomly across 3 billion base pairs of DNA. The totality of these 20,000 genes is termed the ‘exome’. The exome comprises only about 2 per cent of the genome. These genes provide the blueprint for each of the proteins that are collectively responsible for normal cell function, cellular proliferation, cell differentiation and DNA repair. These processes are essential in embryonic development, bodily integrity and our response to internal and external environments.^[3]

Twenty years after the HGP’s completion, clinical genetics has become an informational specialty. Genomic sequencing and its clinical interpretation is, in 2022, the pre-eminent diagnostic modality in clinical genetics and is rapidly becoming a primary foundation for decision-making in precision medicine.

Ethical, legal and social implications

From its inception the HGP established specific provisions for dedicated, funded research on the ethical, legal and social implications (ELSI) of genomic sequencing.^[4] The HGP ELSI Working Group, anticipating the ability of DNA testing to predict a person’s health, recognised the:

‘imperative to protect individuals and society from possible hazards which may be a consequence of our improved ability to detect and predict hereditary illness ... the quantity and complexity of genetic information that should become available requires that special precautions be taken.’^[5]

The Working Group also recognised that ‘deleterious consequences can occur, such as discrimination against gene carriers, loss of employment or insurance, stigmatization, untoward psychological reactions and attention’.^[6]

Such considerations are guiding principles in the everyday practice of genetic medicine. They empower the individual and family to have control over their genetic information within an ethical framework that gives primacy to autonomy alongside beneficence, non-maleficence and justice. A central dictum of genetic counselling in reproductive genetics is one of non-directiveness that is intended to help families and individuals make decisions based upon their own values and beliefs without pressure or coercion.^[7] Nowhere is this more evident than in reproductive decision-making. Nowhere is this more challenged than within the court system.

THE NEED FOR EDUCATION

The judiciary needs to become familiar and informed as to the ‘quantity and complexity of genetic information’ and what constitutes ‘special precautions’. This has been borne out in the materialisation of genetics and genomics in diverse areas of Australian case law over the last three decades. The role of genomics and genetics education programs is equally applicable to the executive branch of government in enacting and refining the development of sound and reasonable policies. This was recognised by the Australian Government with the commissioning of the Australian Law Reform Commission’s (ALRC) report, Essentially Yours: The Protection of Human Genetic Information in Australia (ALRC report), handed down in 2003.^[8] The ALRC report provided a template for the executive to address the concerns of DNA testing across a broad spectrum of established uses and future utilities.

The Terms of Reference for the ALRC report,^[9] like those in its US counterpart, were broad ranging. Of note, they did not explicitly expand upon civil proceedings beyond vesting authority in the ALRC to explore ‘developments in other jurisdictions, including legislative and regulatory action’ and more broadly, any matters it saw fit to advise upon.

‘When the ALRC report was submitted to the Federal Parliament, the use of genetic information in legal proceedings [in Australia] was limited to DNA parentage testing in family law and proceedings related to estates.’^[10] These cases fall within the category of ‘relationship testing’, where DNA testing was used to determine the likelihood of a genetic (biological) relationship between individuals.

At the time of the ALRC report’s release, the US courts had already established the admissibility and utility of DNA testing in cases of failure to warn of the risk of having a child with a serious genetic condition and the negligent administration of DNA testing for genetic disorders.^[11] The ALRC report predicted circumstances that remain relevant in 2023, namely:

‘In practice, the relevance of genetic information in civil proceedings may be limited by current scientific knowledge about the predictive nature of the information; the probabilistic, rather than deterministic, nature of the information; and the existence of other environmental causes of disease in the facts in issue.’^[12]

Not necessarily predicted was the rapid development and immediacy of clinical application of genomic sequencing technologies that enable an entire genome to be sequenced and analysed in less than 24 hours.^[13]

Chapter 46 of the ALRC report identifies various predicted uses of DNA testing in civil proceedings, in relation to:

• Causation: in disproving the plaintiff’s allegation as to the origin of the injury in the establishment of a genetic cause for the plaintiff’s disability.

• Susceptibility: such as genetic susceptibility to chemical, radiation, UV or exposures – based on the egg-shell skull rule.^[14]

• Assumption of risk: based on a known genetic predisposition; that is, contributory negligence or voluntary assumption of risk, such as a breast cancer genetic predisposition where the plaintiff might elect to delay prophylactic risk-reducing breast or ovarian surgery, or the failure to discuss or advise directly as to the importance of prophylactic risk-reducing surgery.

• Assessment of damages: in which the quantum is diminished based on a predisposing or pre-symptomatic condition, such as Huntington disease where the inevitable development of the disease is foreshadowed by the genetic diagnosis results in a shortened lifespan. The difference between predisposition and presymptomatic diagnosis relates to the inevitability of disease onset with age or, in genetic terms, complete versus partial disease ‘penetrance’.^[15] This differs from ‘variable expressivity’ which pertains to when and how a disease may become manifest.

The federal Government’s formal response to the ALRC report^[16] came shortly after the Ipp Review into the law of negligence.^[17] The Government’s position on DNA testing was one of no change to public policy on tort law. At that time – a decade before the emergence of clinical genomic sequencing technologies – it was not clear precisely what was envisioned by the judiciary and the executive on the predicted impact of the era of ‘new genetics’ on either case law or public policy. The federal Government’s response to ch 46 was one that vested authority solely with the judiciary, together with a directive on education:

‘The National Judicial College of Australia and the Law Council of Australia (through its constituent professional associations) should develop and promote continuing legal education programs for judges and legal practitioners, respectively, in relation to the use of genetic information in civil proceedings.’^[18]

This was in contrast to key recommendations in areas such as the accreditation of medical genetic laboratories, the collection and storage of genetic data, health privacy legislation, and discrimination, in response to which regulatory bodies were expected to provide clear guidelines and oversight.^[19]

The NIH/DOE ELSI Working Group identified principles of fairness in the use of genetic information with respect to the criminal justice system^[20] that were not explicitly extended to negligence and malpractice law. Courts have seen fit to uphold adherence to privacy and confidentiality of genetic information in a clinical context.^[21] By way of contrast, court orders and open access to publication of judgments may create a standard that is inadvertently at odds with those in clinical practice. After all, the choice to undertake genetic and genomic testing in fetal medicine and paediatric practice is voluntary and underpinned by the informed consent of the individual, parents or legal guardian.

THE CURRENT STATE OF GENOMIC TESTING

There are currently ~7,000 known genetic disorders.^[22] A large proportion of these are diagnosable from the analysis of ~5,000 genes directly correlated with human disease.^[23] The most common diagnostic modalities in clinical genetic practice are chromosome microarray (CMA) and whole exome sequencing (WES). Both tests are covered by the Medicare rebate. In the case of CMA, many thousands of tests are performed each year in Australia. CMA detects ‘large-scale’ genetic changes, including loss or gain of whole genes or a large part of a gene. It is effectively a street view-like image of the genome in which the genes on a single chromosome are analogous to the buildings in a suburb.

WES is a commonly ordered test to investigate for individual gene sequence variants – disease-associated mutations. These may be sought from a large panel of genes for a defined disorder, such as an ‘intellectual disability panel’, or across the entirety of the exome. WES is analogous to the level of detail provided from a national household census. WES provides the raw sequence via next-generation sequencing (NGS) technologies from a microchip. The next step is ‘bioinformatic’ analysis of the gene sequence using comparison to a standard reference sequence of the human genome. Determining what a gene variant might mean is derived from review of current knowledge from highly curated genomic databases and computer (in silico) prediction programs.

The end result is that ~3 million individual variants in the genome (or ~20,000 in the exome) that exist person-to-person are filtered and distilled into a handful of variants that may be considered causative for the disorder being assessed (termed ‘pathogenic or likely pathogenic variants’ or, in plain English, a mutation). This requires input at the outset detailing the patient’s (or plaintiff’s) clinical phenotype (the individual features derived from a comprehensive history and examination) to know what genes to prioritise in the analysis. The final step is the clinical interpretation – to determine how the genetic diagnosis relates to the clinical features in the affected individual.

The end-to-end process of WES has become subject to ever more rigorous standards as to how variants are categorised and what is reported. There is a high threshold based on strict criteria for a genetic variant to be classified as pathogenic or likely pathogenic. At the other end, it is relatively straightforward to filter out benign person-to-person and population variations.

In clinical practice, the greatest challenge in WES and whole genome sequencing (WGS) interpretation is the genetic variants that are strongly suspected to be causative for the disorder being tested but do not meet strict criteria – ‘variants of uncertain significance’ (VUS). VUS are not considered ‘actionable’ in the clinical setting. Examples of actionable findings are those used for testing in an established pregnancy that might underpin an individual or couple’s decision to continue or terminate a pregnancy. The obvious concern is that a couple might terminate a pregnancy based on the presence of what is later shown to be a harmless genetic variant. Similarly, VUS are not used for ‘cascade’ testing of relatives in a family, such as to provide a predictive cancer genetic susceptibility test.

Pragmatically, a WES report may give:

• a clear positive answer in relation to the indication for testing (a mutation);

• an answer that cannot be defined beyond ‘suspicious’ VUS; or

• a negative ‘non-informative’ test result.

Genomic testing is not a test of exclusion. Accordingly, a negative result is best described as non-informative in the clinician’s interpretation (and medicolegal report). This may be because the disorder results from a gene error in one of the 10,000+ genes for which no human disease has been linked to mutation in that gene, a gene error outside of the region tested or analysed, or a mechanism of disease not discoverable by DNA sequencing.

The incompleteness of current knowledge means that even in disorders such as intellectual disability (ID), cerebral palsy or severe autism spectrum disorder (ASD) for which there is mounting evidence for a genetic basis in the majority of cases, a pathogenic or likely pathogenic result is identified in only up to one quarter to one third of individuals.^[24] The chance of a positive diagnosis is greatest in individuals and families with a previously undiagnosed genetic syndrome such as an ID associated with physical malformations (termed multiple congenital anomaly syndromes). The likelihood may be up to 70 per cent in an individual with severe ID/ASD and congenital anomalies.

GENETIC TESTING AND THE JUDICIARY

The judiciary has acknowledged the central role of genomics, in parallel with its clinical application, in supporting applications for the use of CMA and WES (and now WGS, which has a slightly greater diagnostic yield), along with other specialised DNA testing in medical negligence claims.^[25] Dicta in the intermediate courts, in all determinations to date, have favoured the defendant in seeking approval for court-ordered testing. Landmark cases where judgments for the defendant have ordered the plaintiff to undergo diagnostic genomic testing have typically centred on claims of wrongful birth.

Case law

The first case in which orders were granted for genomic testing was KF By Her Tutor RF v Royal Alexandra Hospital for Children known as the Children’s Hospital Westmead^[26] in 2010. The case centred on the failure to detect the clinical diagnosis of a rare genetic disorder causing hypoglycaemia (PPHI) in the plaintiff in early childhood, which was alleged to have caused recurrent hypoglycaemia, clinical seizures and brain injury. The case was petitioned in a pre-NGS genomic: orders for testing were for CMA and genetic sequencing of a panel of six genes each known to cause PPHI. The testing required blood to be drawn from the plaintiff and for DNA to be sent overseas for testing.

The issue of blood tests in children with needle phobia and anxiety with medical procedures was addressed by Garling J in Plowman v Sisters of St John of God Inc,^[27] where it was pleaded that a chromosome disorder might be anticipated to contribute to the child’s disability but that the testing may cause harm to the child. The use of buccal swabs and salivary samples, which have been in use in clinical practice for over a decade, obviates this concern.

Key considerations in medicolegal testing

Key practical considerations in WES include:

• the cost of testing: in the order of $2,000–$4,000 (or $4,000–$5,000 for WGS);

• the cost of genetic counselling;

• the pros and cons of the inclusion of parental samples, which aid variant filtering, analysis, interpretation and clarity of the final report;

• dicta of the NSW Supreme Court that court-ordered testing be restricted to the plaintiff;^[28]

• delays, typically a few months,^[29] introduced by WES and the accompanying need for pre-test genetic counselling (in accordance with clinical genomic laboratory standards); and

• perhaps most importantly, the potential for confusion as to the utility and outcome of genomic testing to arise at the judicial level.

The latter most often arises from the challenge of clinical interpretation of a VUS.

Further assessment of a VUS might extend to:

• clinical re-evaluation;

• additional non-genetic testing in the proband (the plaintiff);

• the collection and analysis of parental samples for ‘trio WES’ (more commonly included from the outset);

• further genomic laboratory or research-based functional genomic testing; or

• the need to await the accumulation of curated knowledge to definitively interpret a given VUS.

The clinical standard for re-evaluation of a negative exome might be to proceed with WGS (with a ~10–15 per cent additional diagnostic yield) or to simply review the exome data in two years.

It is usual in medicolegal testing to exclude an active search for ‘incidental findings’ by masking the readout from genes associated with risk of cancer, genetic heart disease, neurological disorders, etc. This reduces the risk of ‘off target’ findings that can have health and insurance implications for individuals and family members. Similarly, the issue of genetic relationships such as non-paternity, adoption or even an unexpectedly high degree of relatedness poses a dilemma in genetic counselling and reporting in the context of a birth injury claim where the focus is answering the specific question raised.

Reproductive genetics: An expanding horizon

In fetal medicine, the role of genetic testing for fetal anomaly syndromes is well established. Similarly, in screening for Down syndrome and related disorders of chromosome number, generally it is relatively straightforward to determine the role of genetic screening tests when considering matters such as duty of care and breach. Unsurprisingly, it is not uncommon for such questions to be complicated in the details and circumstances, given the diagnostic overlap and options for non-invasive prenatal screening (NIPS) and first trimester combined screening (FTCS, which assesses neck/nuchal thickness on ultrasound and maternal biochemistry). Both are screening tests that are primarily but not exclusively focused on the risk of Down syndrome (trisomy 21), trisomy 13 and trisomy 18. They may also predict other chromosome disorders and fetal anomalies.

The prior and post-test FTCS/NIPS risks depend on maternal age. The primary referral with an elevated risk of aneuploidy on NIPS/FTCS is generally to fetal medicine services. The next step is counselling on the role and option of a diagnostic genetic test: CMA performed on a chorionic villus sampling (CVS) or amniocentesis sample. This is an essential step for informed genetic counselling and the foundation for decision-making for a woman or couple who might consider termination of pregnancy.

The role of CMA in fetal medicine in the second trimester, led by ultrasound findings, is well established. This is an area that typically requires counselling and a team approach from the fetal medicine specialist, clinical geneticist and genetic counsellor. What is emerging into clinical practice is the prenatal application of ‘ultrarapid WES’ – using DNA from CVS or amniocentesis DNA samples – where a diagnosable genetic disorder is suspected or may be reasonably foreseeable based on ultrasound findings.

Waller v James,^[30] while often viewed through the prism of wrongful life, highlighted the question as to which disorders might be ‘reasonable’ and important to select against in pre-implantation genetic diagnosis (PGD). The case ultimately failed on causation, with the expert consensus that being AT-III deficient was not causal for the extensive intracerebral thrombosis in the plaintiff that led to severe disability. PGD has led to a shift in the threshold and willingness of couples to choose to screen for and select against transfer of an embryo with a predefined genetic disorder. It commonly obviates the dilemma for a couple to choose to test and terminate an established pregnancy.

Genetic carrier screening

Perhaps the most contentious area – which has many parallels to public liability in its scope of duty – is reproductive genetic carrier screening. This testing can be performed preconceptionally or in the first trimester using NGS technology to screen for X-linked and autosomal recessive genetic disorders. These disorders typically occur in a child in the absence of any family history or an identified ethnic-specific risk. Archetypal disorders are cystic fibrosis, fragile X syndrome, spinal muscular atrophy (SMA) and Duchenne muscular dystrophy. In practice, the screening panels in use in 2023 vary from 175–750 genes for conditions predicted to cause serious childhood disease, disability or death. Like NIPS, they are widely available commercially from various providers, may be offered via selected public hospital services, and are relatively costly ($400–$800 for a couple). Expanded carrier panel tests are not currently reimbursed by Medicare or private health insurance.^[31]

The question of scope of liability as to duty of care and breach is broad and most likely contentious in the community, medical profession, judiciary and executive. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists’ (RANZCOG) consensus-based guidelines,^[32] current as of March 2022, state the following:

‘Information on carrier screening for other genetic conditions [beyond conditions such as thalassaemia that are screened for by standard haematology laboratory testing] should be offered to all women planning a pregnancy or in the first trimester of pregnancy. Options for carrier screening include screening with a panel for a limited selection of the most frequent conditions (e.g. cystic fibrosis, spinal muscular atrophy and fragile X syndrome^[33]) or screening with an expanded panel that contains many disorders.’^[34]

While well established as a standard of care in clinical genetics, reproductive genetic carrier screening is by no means established practice with respect to advice given to couples by paediatricians or GPs. The Royal Australian College of General Practitioners’ Guidelines for preventive activities in general practice encourage GPs to talk to women and couples about the option. The Royal Australasian College of Physicians has no specific guidelines.

Reproductive genetic carrier screening was pioneered by private diagnostic laboratories, particularly in the US. In Australia, community awareness has been accelerated with the federal Government’s funding of a national program, Mackenzie’s Mission, named after Mackenzie Casella, who died from the degenerative neuromuscular disorder SMA in 2017. Prior to her birth, Mackenzie’s parents were unaware of the option of reproductive carrier screening.

Mackenzie’s Mission,^[35] administered by Australian Genomics, is seeking to enrol 10,000 couples, offering funded PGD for high-risk couples as a key outcome. Like the private laboratories, it employs high-throughput sequencing technologies with rapid bio-informatic analysis of predefined genes, collated, electronically delivered, individualised (couple) reports and medical supervision for the communication of results and counselling as to the utility of high-risk results. The ease of translation to pre-implantation genetic diagnosis in IVF following a high-risk (1 in 4) result has been a key driver that has altered the threshold and uptake of genetic carrier screening. PGD enables the selective transfer of an unaffected embryo, thereby obviating many of the ethical dilemmas of genetic testing in the midst of a pregnancy and decision-making on termination versus continuation of an affected pregnancy.

Reproductive genetic screening creates a novel dilemma for the medical profession. To not advise on carrier screening can give rise to a breach in duty of care for which the seriousness of the disease or disability translates to large claims for damages in which causation may be incontestable. Reproductive genetic carrier screening, and current practical limitations in the application of WES sequencing in paediatric and fetal medicine, creates foreseeability for negligence claims. How the intermediate and higher courts, and potentially Government, will respond to this remains to be determined.

CONCLUSION

The advent of genomics has seen a paradigm shift from genetic testing as a niche practice to a part of everyday clinical medicine. This is paralleled within the law, with genomic sequencing firmly entrenched in the defence of wrongful birth claims and an ever-increasing scope of duty of care, breach and foreseeability. The judiciary needs to become intimately familiar with core elements of the principles and practise of clinical genomics in its application to case law. What remains to be seen is how the higher courts will treat the ever-widening questions arising from dicta within lower and intermediate courts and whether the executive might seek to rein in the scope of duty of care.

Dr Ken Maclean is a clinical geneticist in private practice with an active interest in reproductive genetics, its clinical applications and health law.

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^[1] US Department of Health and Human Services and US Department of Energy, ‘Understanding our genetic inheritance: The Human Genome Project, the first five years, FY 1991–1995’, NIH Publication No. 90-1590 (April 1990) (Human Genome Project)

<https://web.ornl.gov/sci/techresources/Human_Genome/project/5yrplan/firstfiveyears.pdf>.

^[2] International Human Genome Sequencing Consortium, ‘Finishing the euchromatic sequence of the human genome’, Nature, Vol. 431, October 2004, 931–45.

^[3] WT Boyce, MB Sokolowski and GE Robinson, ‘Genes and environments, development and time’, Proceedings of the National Academy of Sciences of USA, Vol. 117, No. 38, 22 Sep 2020, 23235–41; MF Donovan and M Cascella, ‘Embryology, Weeks 6-8’ (Updated 10 Oct 2022), StatPearls [Internet], Treasure Island (FL): StatPearls Publishing, Jan 2022.

^[4] Human Genome Project, above note 1, ‘Executive Summary’, viii; ‘Scientific goals ethical, legal and social considerations’, 20.

^[5] Human Genome Project, above note 1, ‘Report of the Working Group on Ethical, Legal and Social Issues related to mapping and sequencing the human genome', app 7, 65.

^[6] Ibid.

^[7] H Skirton, C Cordier, C Ingvoldstad et al, ‘The role of the genetic counsellor: A systematic review of research evidence, European Journal of Human Genetics, Vol. 23, 2015, 452–8; G Elwyn, J Gray and A Clarke, ‘Shared decision making and non-directiveness in genetic counselling’, Journal of Medical Genetics, Vol. 37, 2000, 135–8.

^[8] Australian Law Reform Commission, Essentially Yours: The Protection of Human Genetic Information in Australia (Report 96, 28 March 2003) (ALRC report).

^[9] Ibid, Terms of Reference, 13–8.

^[10] Ibid, 35.44–8. See also Roche v Douglas [2000] WASC 146; (2000) 22 WAR 331.

^[11] Ibid, 46.1–3. See DE Hoffmann, and KH Rothenberg, ‘Judging genes: Implications of the second generation of genetic tests in the courtroom’, Maryland Law Review, Vol. 66, No. 4, 2007, 858–922; G Marchant, ‘Genetics and toxic torts’, Seton Hall Law Review, Vol. 31, 2001, 949; J Wriggins, ‘Genetics, IQ, determinism and torts: The example of discovery in lead exposure litigation’, Boston University Law Review, Vol. 77, 1997, 1025.

^[12] ALRC report, above note 8, 46.4.

^[13] CJ Saunders, NA Miller, SE Soden et al, ‘Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units’, Science Translational Medicine, Vol. 4, No. 154, 3 Oct 2012, 154ra135.

^[14] R v Blaue [1975] EWCA Crim 3; (1975) 61 Cr App R 271.

^[15] This differs from expression, which pertains to when and how a disease might be manifest.

^[16] Australian Government, Full Australian Government Response to ALRC Report 96 (18 October 2010) <https://www.alrc.gov.au/inquiry/protection-of-human-genetic-information/full-australian-government-response-to-alrc-report-96/>.

^[17] Commonwealth of Australia, Review of the Law of Negligence: Final Report (September 2002) (Ipp Review).

^[18] Australian Government, above note 16, rec 46-1.

^[19] ALRC report, above note 8, ‘Executive Summary’, ch 7, 35.

^[20] Human Genome Project, above note 1, ‘Report of the Working Group on Ethical, Legal and Social Issues related to mapping and sequencing the human genome', app 7, 67.

^[21] ABC v St George's Healthcare NHS Trust [2017] EWCA Civ 336; [2017] PIQR P15, EWCA Civ 336.

^[22] RJ Pengelly, D Ward, D Hunt et al, ‘Comparison of Mendeliome exome capture kits for use in clinical diagnostics’, Scientific Reports, Vol. 10, 2020.

^[23] Ibid.

^[24] KM Bowling, ML Thompson, MD Amaral et al, ‘Genomic diagnosis for children with intellectual disability and/or developmental delay’, Genome Medicine, Vol. 9, No. 1, 2017, 43; S Srivastava, JA Love-Nichols, KA Dies et al, ‘Meta-analysis and multidisciplinary consensus statement: Exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental’, Genetics in Medicine, Vol. 21, No. 11, 2019, 2413–21.

^[25] For example, Fragile X DNA testing.

^[26] [2010] NSWSC 891.

^[27] [2014] NSWSC 333. Also see Boral Transport Pty Ltd v Gulic [2013] NSWCA 150; Hamilton v State of New South Wales [2013] NSWSC 1437; KF By Her Tutor RF v Royal Alexandra Hospital for Children known as the Children’s Hospital Westmead [2010] NSWSC 891; Emma Jane Plowman by her next friend Toby Plowman v Sisters of St John of God Inc [2012] NSWSC 376;

Rowlands v State of New South Wales [2009] NSWCA 136.

^[28] Wells by his tutor McGuffog v Hunter New England Local Health District [2018] NSWSC 1877, [114].

^[29] Laboratory standards for WES are within a 100-day reporting time for samples that are not clinically urgent and ~14 days for CMA.

^[30] [2006] HCA 16.

^[31] Department of Health and Aged Care, ‘New help for Australians on the IVF journey’ (Media release, 24 October 2021) <https://www.health.gov.au/ministers/the-hon-greg-hunt-mp/media/new-help-for-australians-on-the-ivf-journey>.

^[32] RANZCOG, Genetic carrier screening (March 2022) <https://ranzcog.edu.au/wp-content/uploads/2022/05/Genetic-carrier-screeningC-Obs-63New-March-2019_1.pdf>.

^[33] Department of Health and Aged Care, above note 31.

^[34] Ibid, 8.

^[35] See <https://www.mackenziesmission.org.au>.