Variable approaches to genetic counseling for microarray regions of homozygosity associated with parental relatedness

Abstract

SNP microarrays are capable of detecting regions of homozygosity (ROH) which can suggest parental relatedness. This study was designed to describe pre- and post-test counseling practices of genetics professionals regarding ROH, explore perceived comfort and ethical concerns in the follow-up of such results, demonstrate awareness of laws surrounding duty to report consanguinity and incest, and allow respondents to share their personal experiences with results suggesting a parental relationship. A 35 question survey was administered to 240 genetic counselors and geneticists who had ordered or counseled for SNP microarray. The results are presented using descriptive statistics. There was variation in both pre- and post-test counseling practices of genetics professionals. Twenty-five percent of respondents reported pre-test counseling that ROH can indicate parental relatedness. The most commonly reported ethical concern was disclosure of findings suggesting parental relatedness to parents of the patient; only 48.4% reported disclosing parental relatedness when indicated. Fifty-seven percent felt comfortable receiving results suggesting parental consanguinity while 17% felt comfortable receiving results suggesting parental incest. Twenty percent of respondents were extremely/moderately familiar with the laws about duty to report incest. Personal experiences in post-test counseling included both parental acknowledgement and denial of relatedness. This study highlights the differences in genetics professionals' pre- and post-test counseling practices, comfort, and experiences surrounding parental relatedness suggested by SNP microarray results. It identifies a need for professional organizations to offer guidance to genetics professionals about how to respond to and counsel for molecular results suggesting parental consanguinity or incest.

Regions of homozygosity identified by oligonucleotide SNP arrays: evaluating the incidence and clinical utility

“…It is increasingly becoming a challenge about how to respond to and counsel for such results, and a need for genetics professionals to have a guideline has been requested. 18 The ethical, legal and social outcomes that these cases present and the approaches to dealing with the same are still evolving. 18,19 In the sibling studies, the result showed only 13 of 23 families (B57%) had a concordant result in prediction of parental relatedness.…”

“…18 The ethical, legal and social outcomes that these cases present and the approaches to dealing with the same are still evolving. 18,19 In the sibling studies, the result showed only 13 of 23 families (B57%) had a concordant result in prediction of parental relatedness. Although in some families such as family 3 (Table 1b), three siblings had almost exact amount of ROHs (B876 Mb), for other families, ROH from one sibling alone will not reliably predict the degree of relatedness between parents.…”

Detection and Reporting of Homozygosity Associated with Consanguinity in the Clinical Laboratory

“…As SNP microarray is still a relatively new technology, clinician interpretation of these results and patient care related to results of homozygosity are quite variable. Clinician follow-up for results of homozygosity was the focus of the survey by Grote et al [15] . The study assessed clinician comfort level in receiving/ reporting results of homozygosity, pre-and post-test counseling for microarray results of homozygosity, patient reactions to results of homozygosity, and physician understanding of laws related to the duty to report incest.…”

“…The American College of Medical Genetics and Genomics (ACMG) issued a guidance document in 2013 which focused on detection and downstream communications with ordering clinicians [12] . These guidelines as well as other publications have addressed the essential role of pre-test counseling for patients and their families ensuring that families understand that SNP microarray testing can reveal consanguinity [15,16] . The ACMG guidelines also recommend that each laboratory should establish a size threshold for inclusion of ROH in genomic calculations, suggesting 2-5 Mb as a potential threshold, excluding the X chromosome.…”

“…While the ACMG guidelines use 10% as the threshold value above which clinical reports should indicate a possible first-or second-degree relationship, most surveyed laboratories quoted >20% as indicative of incest. Less than one third of the surveyed laboratories used a threshold of 12.5%, the coefficient of inbreeding for second-degree relatives [15] .…”