Recurrent Rearrangements of Chromosome 1q21.1 and Variable Pediatric Phenotypes

Abstract

BACKGROUND-Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients.

1q21.1 Microduplication expression in adults

“…1,2,[5][6][7][8][9][10][11][12] We also examined primary articles and reviews of CNVs in autism, 13 schizophrenia, 14 mental retardation, 15 and congenital heart disease 16 for references to studies reporting subjects with 1q21.1 duplications. [17][18][19][20] Other citations involving 1q21.1 duplication cases were also assessed.…”

“…3,35 We systematically reviewed 28 primary reports identified and their accompanying supplemental materials to identify unique individuals and abstract as much information as possible on each subject. 1,2,[5][6][7][8][9][10][11][12][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Any subjects with 1q21.1 duplications that were not 1.0-5.0 Mb (Figure 1) in size were excluded, 12,31 allowing us to include atypical variants that were larger or smaller than the standard duplication classes used in our analyses. We documented the ascertainment criteria, country of origin, authors, and the demographic, clinical, and genotypic characteristics of subjects in different studies, and used these variables to attempt to identify duplicate cases reported in two or more papers.…”

“…Four studies were excluded because the sources of subjects overlapped with those of other reports and/or the origin of cases was not specified. 17,18,32,34 We compiled data for 107 subjects from the remaining 22 studies 1,2,[5][6][7][8][9][10][11][19][20][21][22][23][24][25][26][27][28][29][30]33 for the main analyses in this report.…”

“…Although incomplete penetrance and variable expressivity are common to deletions and duplications at the 1q21.1 locus, initial reports have suggested that the deletion has a relatively more consistent pattern of expression including microcephaly, developmental abnormalities, and schizophrenia. 1,2 The 1q21.1 duplication was the 11th most common of 28 genomic disorders reported in a recent laboratory survey of clinical microarray results. 3 Consistent with the general tendency for duplications to be less deleterious than deletions and a corresponding ascertainment bias in clinical samples, 4 the 1q21.1 duplication may be rarer than the reciprocal deletion in many, but not all, clinical settings.…”

“…1,2 Other genomic disorders (e.g., 22q11.2 deletion syndrome) have an adult phenotype that differs from the pediatric phenotype. Growing use of clinical genome-wide microarrays to investigate CNVs has meant increasing pressure for more information on the lifetime expression of 1q21.1 duplications to better inform individuals found to have this CNV, their families, and clinicians.…”