Jacobsen Distal 11q Deletion Syndrome study with WGS data on dbGaP (1 participants)

phs002036 — Chromoanasynthesis as a Cause of Jacobsen Syndrome

<p>Jacobsen syndrome (<a href="https://www.omim.org/entry/147791">OMIM #147791</a>) is a rare multisystem genomic disorder involving craniofacial abnormalities, intellectual disability, other neurodevelopmental defects and terminal truncation of chromosome 11q, typically deleting ~170 to >340 genes. We describe the first case of Jacobsen syndrome caused by congenital chromoanasynthesis, an extreme form of complex chromosomal rearrangement. Six duplications and five deletions occurred on one copy of chromosome 11q with microhomology signatures in the breakpoint junctions, indicating an all-at-once replication-based rearrangement mechanism in a gametocyte or early post-zygotic cell. Eighteen genes were deleted from the Jacobsen region, including <a href="https://www.ncbi.nlm.nih.gov/gene/84623">KIRREL3</a>, which is associated with intellectual disability.</p> <p> Patients of any age with abnormal immune function who have recurrent or unusual infections, whose blood tests show evidence of immune dysfunction, or who have GVHD, XSCID, CGD or LAD may be eligible for this study. Patients' parents, siblings, grandparents, children, aunts, uncles and first cousins of any age also may be included. Healthy normal volunteers between 18 and 85 years of age are recruited as controls. </p>