Abstract
We present a case of 9p- syndrome with a complex chromosomal event originally characterized by the classical karyotype approach as 46,XX,der(9)t(9;13)(p23;q13). We used advanced technologies (Bionano Genomics genome imaging and 10× Genomics sequencing) to characterize the location of the translocation and accompanying deletion on Chromosome 9 and duplication on Chromosome 13 with single-nucleotide breakpoint resolution. The translocation breakpoint was at Chr 9:190938 and Chr 13:50850492, the deletion at Chr 9:1-190938, and the duplication at Chr 13:50850492-114364328. We identified genes in the deletion and duplication regions that are known to be associated with this patient's phenotype (e.g., ZIC2 in dysmorphic facial features, FOXD4 in developmental delay, RNASEH2B in developmental delay, and PCDH9 in autism). Our results indicate that clinical genomic assessment of individuals with complex karyotypes can be refined to a single-base-pair resolution when utilizing Bionano and 10× Genomics sequencing. With the 10× Genomics data, we were also able to characterize other variation (e.g., loss of function) throughout the remainder of the patient's genome. Overall, the Bionano and 10× technologies complemented each other and provi...Continue Reading
References
Nov 1, 1988·Journal of Medical Genetics·J L HuretJ Lejeune
Oct 16, 1999·American Journal of Human Genetics·L A ChristS Schwartz
Jan 19, 2006·American Journal of Medical Genetics. Part a·Hiroki KawaraNaomichi Matsumoto
May 3, 2008·American Journal of Medical Genetics. Part a·Mariëlle E M SwinkelsConny M A van Ravenswaaij-Arts
Jul 22, 2008·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Xueya HaugeChrista Lese Martin
Jul 21, 2010·Genome Research·Aaron McKennaMark A DePristo
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Jun 26, 2012·Fly·Pablo CingolaniDouglas M Ruden
Dec 15, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Weimin BiSau Wai Cheung
Mar 14, 2013·Congenital Anomalies·Norimasa MitsuiHirofumi Ohashi
Jul 16, 2014·Nature Genetics·Andy RimmerGerton Lunter
Aug 16, 2017·BMC Genomics·Giulia BabbiRita Casadio
Nov 3, 2017·Bioinformatics·Brent S Pedersen, Aaron R Quinlan
Jul 18, 2018·Nature Methods·Sangtae KimChristopher T Saunders
Jul 4, 2019·The New England Journal of Medicine·Evan E Eichler
Sep 5, 2019·Genome Research·Wolfram DemaerelJoris R Vermeesch
Dec 31, 2019·Advances in Experimental Medicine and Biology·Stephen P DaigerEric A Pierce