Single variant, yet "double trouble": TSC and KBG syndrome because of a large de novo inversion.

Despite the advances in high-throughput sequencing, many rare disease patients remain undiagnosed. In particular, the patients with well-defined clinical phenotypes and established clinical diagnosis, yet missing or partial genetic diagnosis, may hold a clue to more complex genetic mechanisms of a disease that could be missed by available clinical tests. Here, we report a patient with a clinical diagnosis of Tuberous sclerosis, combined with unusual secondary features, but negative clinical tests including and Short-read whole-genome sequencing combined with advanced bioinformatics analyses were successful in uncovering a de novo pericentric 87-Mb inversion with breakpoints in and , which explains the TSC clinical diagnosis, and confirms a second underlying monogenic disorder, KBG syndrome.

Evaluation of a decision aid for families considering p53 genetic counseling and testing.

Purpose: Li-Fraumeni syndrome (LFS) is associated with p53 germline mutations, and carriers are at increased risk for multiple primary cancers. We evaluated outcomes following the administration of a video-based decision aid (DA) prior to clinical p53 genetic counseling and testing among persons who had previously participated in cancer genetics research.

Methods: Fifty-seven individuals at risk for a known p53 mutation completed baseline and post-DA measures of psychological outcomes, plus knowledge and attitudes regarding p53 genetic testing.