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Study Finds Variability in How Labs Report Consanguinity Identified by SNP Arrays


A recent survey has found that laboratories differ in how they report findings indicating parental relatedness back to clinicians caring for patients with constitutional abnormalities.

The survey was carried out by geneticists at Cincinnati Children's Hospital Medical Center, and focused on how the occurence of regions of homozygosity detected by SNP microarrays is reported to clinicians.

The study is described in a paper in Genetics in Medicine this month.

"We were trying to figure out how labs are handling this information," said Kristen Sund, a genetic counselor at CCHMC and corresponding author on the paper.

Sund told BioArray News that she and her coauthors set out to determine what kinds of information is being included in lab reports, such as whether or not labs are mentioning the possibility that the parents of the affected individual could be related, and what they are doing if there are results that indicate there was some kind of incestuous relationship.

In total, 18 laboratories that offer SNP array-based constitutional testing were queried on how they report ROH back to clinicians. According to the paper, while all those surveyed said they felt obligated to report ROH results that suggest uniparental disomy, the labs differed when it came to how that information was presented.

"Only about half of the labs put the percent of homozygosity in the report," Sund noted. "And only two laboratories mentioned what they thought the relationship [between the parents] might be, and I think that's where things get a little sketchy, because we still don't have standards for how to do these calculations," she said.

Unlike comparative genomic hybridization arrays, SNP arrays can detect regions of homozygosity that can imply uniparental disomy or parental consanguinity, including incest. Because of this, the CCHMC researchers only surveyed labs that use SNP arrays. Of the 18 respondents, 14 said they used the Affymetrix platform and four said they used the Illumina platform. Eleven were lab directors, six were genetic counselors, and one was a clinical geneticist.

According to the paper, there were a number of ways in which the labs differed when it came to reporting ROH results.

For example, there were different cutoff standards for reportable size, both for UPD and for ROH; different cutoff standards for size of ROH used in calculating percentage of homozygosity; and the use of either the whole genome or the autosome as the basis for calculating percentage of homozygosity.

There were also differences in the follow-up practices when ROH findings suggested parental relatedness.

For instance, 23 percent said they felt it was their duty to report such results only in cases of incest — generally thought of as a first-degree relationship — but not in situations where the parents were likely to be more distantly related.

Another 23 percent said they had a duty to report such findings because of "legal and ethical issues," such as a duty to report child abuse. Of the remaing respondents, 23 percent said they were generally notified of a parental relationship, if any, ahead of testing; 15 percent said they notified clinicians of any abnormal finding; and 15 percent said that reporting back such results were a "medical necessity," as the result could influence a diagnosis or future family planning.

Ten of the respondents, or 56 percent, said that they always contacted the ordering health-care provider when consanguinity was revealed. Of these, four had the practice of recommending that the ordering physician should take additional steps such as performing clinical testing for a recessive disorder suggested by the phenotype observed and the ROH found.

None of the laboratories surveyed directly contacted the legal authorities, social work teams, or an ethics board, the authors noted in the paper. Instead, the majority of respondents said that they have contacted the ordering health-care provider in cases of suspected incest.

A Need for Guidelines

According to Sund, the results of the survey suggest that there is a need for guidelines on how to handle such cases, and she noted that the American College of Medical Genetics is already drafting such recommendations.

"I do think this has forced our laboratory directors to look at things differently," Sund said of the survey, "but I think most labs will wait for the [ACMG] guidelines."

According to the paper, such guidelines should help laboratories to "address the legal and ethical dilemmas that may arise" from SNP array-based testing and "ensure consistency" in reporting and follow-up and enable laboratories to take the recommended steps whenever genetic testing suggests parental consanguinity or incest. "It is imperative that the genetics community develop guidelines to address these concerns, both in the laboratory and in the clinic," the authors concluded.

Hutton Kearney, cytogenetics director at Mission Health in Asheville, NC, told BioArray News this week that a draft of these guidelines is currently out for ACMG membership comment and could become available later this year.

Over the next several weeks, the college will collect comments or dissension from the ACMG membership, Kearney said. Following any recommended changes to the guideline, the ACMG board of directors will have to approve the guidelines for distribution to the general public. This will likely take at least another month, she added.

Cytogeneticists have been clamoring for guidelines on handling cases of suspected incest or cosanguinity for several years. Last year, researchers at Baylor College of Medicine recommended that healthcare institutions establish a committee to draft guidelines that deal with issues of consent and reporting of incestuous parental relationships.

They also suggested at the time that existing ethics committees associated with the American College of Medical Genetics, the American Society of Human Genetics, and the European Society of Human Genetics could also draft such guidelines (BAN 2/15/2012).

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