Currents in contemporary bioethics. Identifying consanguinity through routine genomic analysis: reporting requirements.

摘要: Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from more targeted single-gene last decade. Chromosomal microarray (CMA) now first line test for multiple birth defects, intellectual impairment (including autism), an unusual constellation symptoms do not fit known disease.1 There three types CMA currently clinically available. by oligonucleotide array-based comparative hybridization (aCGH) compares signal patient’s DNA reference sample each on array. Depending specific array, this can range tens thousands hundreds oligonucleotides. A relative loss interpreted as deletion, whereas gain duplication (or, in rare cases, triplication quadruplication). aCGH detect very small losses gains typically uncovers genetic abnormalities about 10–20% cases.2 single nucleotide polymorphism (SNP) uses completely technology genotype individual at millions nucleotides commonly polymorphic genome. Gains detected increases decreases SNP other SNPs well genotypes seen located tandem genome.3 Like aCGH, will DNA, but it sometimes miss changes detect. However, analysis, unlike also areas where chromosome pairs parts identical one another. Most recently, hybrid arrays have been developed combine both technologies into test. Since copy pair chromosomes inherited mother father, when (i.e., there absence heterozygosity (AOH)), two possibilities. If only involved, then cause could either be uniparental isodisomy (meaning child copies parent no same parent), distant consanguinity parents blood relatives).4 must relatives The closeness relationship between estimated based number size blocks identical. Analysis parental samples required make determination, confirm finding conclusively identify father child. In February 2011, our colleagues Baylor College Medicine (BCM) reported several disability who were referred whom revealed large regions AOH chromosomes.5 Since publication, clinicians BCM total seven SNP-analysis accounting 19–25% genome, which consistent was conceived first-degree parent-child full siblings) (Table 1). ranged age newborn 11 years old. None mothers themselves under 18 time testing, least four minors conceived. In 2 7 cases suspected prior testing. As common practice many states, performed without requirement informed consent, so possibility identifying addressed receiving results, unless already suspected. all these questions raised whether physicians had obligation report findings Child Protective Services (CPS) doing would unethical breach patient confidentiality. Table 1 Cases First-Degree Consanguinity Identified through Analysis Informed Consent Testing The U.S. does uniform federal policy requiring consent clinical Requirements obtaining legally adequate generally determined state law. majority (n=37) including Texas, require order test6 because considered routine diagnostic authorized general treat patients sign upon admission hospital clinic. Out thirteen states inconsistencies exist what information should disclosed.7 Six written document remaining expressly list include.8 These that, minimum, form explain purpose test, intended derived, description conditions tested for.9 Not surprisingly, specifically addresses lead suspicion abuse if minor, triggering mandated reporting requirements. With emergence new technologies, like CMA, increasingly reveal relevant incidental findings, unanticipated variants uncertain significance directly related phenotype. some may choose receive information, especially immediately actionable. much debate how authority decisions behalf their minor children.10 however, right refuse child, result serious harm imminent death. decision, important adequately risks benefits potential (like AOH) significance. necessarily follow discovering disclosed. For most patients, irrelevant unnecessary anxiety even refusal test. Further, abuse. Consider, example, chest X-rays present emergency department respiratory issues. Parents results x-ray (if, unexpected rib fractures discovered), trigger mandatory reporting. Rather, issue dealt usually consultation experts. This approach, avoids protects victims abuse, adopted context