New Genetic Variants Identified for Bloom Syndrome

(Cambridge, MA, USA) conducted an extensive literature review and examining sequence-based, laboratory and bioinformatics evidence. Study participants were 22,864 ethnically diverse individuals referred by fertility clinics from across the USA for routine carrier screening between April 2012 and February 2014. Informed consent processes were followed for each patient.

The investigators identified 50 genetic variants of the gene for Bloom syndrome (BLM) that it deemed pathogenic, or associated with Bloom syndrome. The literature review turned up 76 variants, but some were excluded from the test's list of pathogenic sequences following further scrutiny by the scientists. During screening, they detected 39 carriers of 11 different mutations that it had previously identified as pathogenic. Using a subset of the data, the company found the carrier rate to be 1/510 subjects, consistent with the expected ratio based on prior knowledge.

The team identified 16 novel "truncating" variants that can be identified as pathogenic by their genetic sequence alone, and do not require laboratory experiments or statistical evidence to prove their association with the disease. More than a quarter of the carriers (28%) had one of the previously unidentified truncating genetic variants. About 40% of all carriers of Bloom syndrome genes had a known pathogenic variant that, to their knowledge, that was not included in any other commercial carrier screening test.

The authors concluded that their data indicate that using a comprehensive panel of rigorously evaluated variants for carrier screening a pan-ethnic population provides major advantages in terms of increased rates of carrier detection. Limited genotyping panels would have missed the carrier status of many of the individuals they identified because they were not carriers of the major ethnically specific common variants. The study was published online on April 23, 2015, in the journal Molecular Genetics & Genomic Medicine.

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