Structural Variation Sequencing of 26 Amniotic Fluid Samples With Partial Gene Duplications and Postnatal Follow-Up of the Fetuses

Structural variation sequencing (mate-pair) resolving partial gene duplication structure in amniotic fluid

Structural variation sequencing (SVseq, mate-pair library) was applied retrospectively to 26 amniotic fluid samples with partial gene duplications initially detected by microarray or sequencing. The method resolved the duplication structure in all 26 cases: 84.6% tandem duplications, 11.5% complex rearrangements, and one case with no actual duplication. Among tandem duplications, 13 extragenic ones preserving gene integrity were classified benign or VUS, and 9 intragenic ones disrupting gene structure were classified pathogenic/likely pathogenic or VUS. Postnatal follow-up revealed an abnormal phenotype in only two intragenic cases. SVseq enables confident pathogenicity assessment and clear genotype-phenotype correlation prenatally.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The structural distinction between intragenic duplications (potentially deleterious) and extragenic ones (preserving the gene) resolves a daily, anxiety-inducing problem in prenatal counseling when facing a partial duplication of uncertain significance. Breakpoint resolution by mate-pair provides a level of evidence that microarray alone cannot. A method directly integrable into prenatal diagnostic protocols.