The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system

A reference data set of 5.4 million phased human variants validated by genetic inheritance from sequencing a three-generation 17-member pedigree

“…S10), which is consistent with the occurrence of both somatic deletions and germline deletions or duplications (but does not meet the criteria for inclusion in Categories 1-3). An example of a complex event is shown in Figure 3C, in which somatic instability in different individuals has occurred in 22q11.2, a region in the genome that is known to be highly mutable (Mikhail et al 2014). Additionally, there are approximately 589 SNVs in 322 clusters that failed to match the inheritance vectors, that is consistent with a double crossover or gene conversion (Supplemental Table S14).…”

22q11.21 Deletion Syndromes: A Review of Proximal, Central, and Distal Deletions and Their Associated Features

“…c Data from Rauch et al, 1999Rauch et al, , 2005Saitta et al, 1999;Mikhail et al, 2007Mikhail et al, , 2014Ben-Shachar et al, 2008;Jalali et al, 2008;Rødningen et al, 2008;Xu et al, 2008;Ogilvie et al, 2009;Bruce et al, 2010;Madan et al, 2010;Garavelli et al, 2011;Tan et al, 2011;Verhoeven et al, 2011;Yu et al, 2011;Breckpot et al, 2012;Fagerberg et al, 2013;Molck et al, 2013;Rump et al, 2014. d Data from Shaikh et al, 2000;Rauch et al, 2005;Nik-Zainal et al, 2011;Yu et al, 2011;Mikhail et al, 2014. e Data from Wieser et al, 2005;Jackson et al, 2007;Lafay-Cousin et al, 2009;Beddow et al, 2011;Bourdeaut et al, 2011;Tan et al, 2011;Toth et al, 2011. f Index cases and familial carriers.…”

“…Based on the classification system of Mikhail et al [2014] and the clinical issues unique to distal type I deletion carriers, we include deletions spanning LCR22C-E (C-E) with the type I group [Ogilvie et al, 2009;Garavelli et al, 2011;Breckpot et al, 2012;Mikhail et al, 2014;Rump et al, 2014]. The reported deletions have largely been de novo and fetuses/neonates having distal type I deletions tended to require pregnancy and delivery management that individuals with the other types of deletions typically do not ( table 3 ).…”

“…In the studies by Rump et al [2014], Breckpot et al [2012], Ogilvie et al [2009], and Garavelli et al [2011], the authors also included individuals with deletions spanning LCR22C-E (C-E) in the central group. Given the similarity between those individuals and individuals with distal type I deletions as described in Mikhail et al [2014], we propose that deletions spanning C-E be classified as distal type I deletions and have included them in the next section.…”

“…Deletions of more distal regions have also been reported extensively, and many of those individuals were referred for suspicion of DGS, highlighting the similarity of phenotypic features for these CNVs [Kurahashi et al, 1996;Rauch et al, 1999Rauch et al, , 2005Saitta et al, 1999;Shaikh et al, 2000;Garcia-Miñaur et al, 2002;Wieser et al, 2005;Jackson et al, 2007;Mikhail et al, 2007Mikhail et al, , 2014Ben-Shachar et al, 2008;Jalali et al, 2008;Rødningen et al, 2008;Xu et al, 2008;Lafay-Cousin et al, 2009;Ogilvie et al, 2009;Bruce et al, 2010;Madan et al, 2010;Beddow et al, 2011;Bourdeaut et al, 2011;Eaton et al, 2011;Garavelli et al, 2011;Nik-Zainal et al, 2011;Tan et al, 2011;Toth et al, 2011;Verhoeven et al, 2011;Yu et al, 2011;Breckpot et al, 2012;Pebrel-Richard et al, 2012;Verhagen et al, 2012;Fagerberg et al, 2013;Zhao et al, 2013;Rump et al, 2014;Racedo et al, 2015]. The literature for these other CNVs is not uniform with respect to the designation of particular intervals, and previous reviews have grouped proximal and distal CNVs together [Tan et al, 2010;Yu et al, 2011].…”