Mosaicism for an ectopic NOR at 8pter and a complex rearrangement of chromosome 8 in a patient with severe psychomotor retardation

Abstract

We describe a 3-year-old girl with severe delays in mental and motor skills, a history of generalized seizures, and subtle dysmorphic features. Conventional cytogenetics revealed a mosaic karyotype. A de novo ectopic NOR at the telomeric region of the short arm of one chromosome 8 (8ps) was found in 90% of lymphocyte and in 98% of fibroblast metaphases. A small NOR-bearing marker chromosome and a large derivative chromosome 8 without short arm satellites (der(8)) were present in the remaining cells. FISH with a probe specific for centromeres 14 and 22 labeled both the telomeric region of 8ps and the small marker centromere. Der(8) included an inverted duplication of 8p and a rearranged duplication of 8q but lacked a second centromere. A subtelomeric probe for 8p revealed a cryptic deletion in 8ps and der(8). Thus, the karyotype represents a combination of submicroscopic partial monosomy 8pter and mosaic trisomy 8.

Telomere Capture as a Frequent Mechanism for Stabilization of the Terminal Chromosomal Deletion Associated with Inverted Duplication

“…Although the Utype exchange (mechanism 3) is the most frequent inv dup del mechanism in all other chromosome arms [Rowe et al, 2009], the majority of reported inv dup del(8p) can be explained by the mechanisms 1 or 2 mentioned above ( fig. 4 ; table 3 ) [Weleber et al, 1976;Dill et al, 1987;Minelli et al, 1993;Barber et al, 1994;de Die-Smulders et al, 1995;Guo et al, 1995;Floridia et al, 1996;Macmillin et al, 2000;Giglio et al, 2001;Pabst et al, 2003;Felbor et al, 2004;Shimokawa et al, 2004Shimokawa et al, , 2005Cooke et al, 2008;Zuffardi et al, 2009] with few exceptions [Buysse et al, 2009;Rowe et al, 2009]. In this study, the formation of the inv dup del(8p) appears to be caused by mechanism 2 in patient 2, and by mechanism 3 in patient 3 ( fig.…”

Genomic profile of copy number variants on the short arm of human chromosome 8

“…[2][3][4][5][6] These REPD-and/or REPP-related 8p genomic rearrangements include (1) the 8p23.1 deletion or duplication between REPD and REPP, [6][7][8][9] (2) the 8p23.1 paracentric inversion between REPD and REPP, 8,10 (3) the pericentric inversion (inv(8)(p23.1q22.1)) and recombinant chromosome 8 (rec (8)dup(8q)inv(8)(p23.1q22.1)), 11 (4) the 8p interstitial inverted duplication with associated terminal deletion (inv dup del(8p)), 5,6,8,10,[12][13][14][15][16][17][18][19][20][21][22][23][24] (5) the 8p translocations involving the 8p23.1, 25,26 and (6) different types of supernumerary chromosome 8 (SMC (8)) involving the breakpoints within 8p23.1. 4,27 In addition to these defined 8p genomic abnormalities, other pathogenic genomic changes have been identified, [28][29][30] whereas numerous genomic imbalances on 8p are still described as copy number variants (CNVs) of unknown clinical significance or CNVs without apparent clinical significance (benign CNVs) (http://projects.tcag.ca/variation).…”