A CNV Catalogue
Rapid incorporation of microarray analysis/aCGH for studies of children with developmental disabilities and its endorsement as a first-tier test for these children [1 ] has yielded a vast number of subtle chromosome changes that were unseen by routine kar
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A CNV Catalogue
Rapid incorporation of microarray analysis/aCGH for studies of children with developmental disabilities and its endorsement as a first-tier test for these children [1] has yielded a vast number of subtle chromosome changes that were unseen by routine karyotyping. This increase in resolution has escalated a difficulty that is the main theme of this book, namely, to distinguish which changes—i.e., extra or missing small segments of DNA or copy number variants (CNVs)—contribute to symptoms (are pathogenic) and which are circumstantial (benign variations). As discussed in Chap. 9, reporting a CNV as the cause of disease, so important for diagnosis and genetic counseling, is empiric and emergent, primarily based on its association with recurring patterns of malformation and mental disability. From accumulating patient databases have come standard criteria [2] for pathogenesis, including: 1. Recurring association with a distinctive clinical pattern or syndrome, as for velocardiofacial syndrome with 22q11 microdeletion 2. Size above 500 kb 3. Presence of genes within the aneuploid interval, particularly when they have known functions that relate to patient findings 4. Presence in the affected child but not in normal relatives, and, extrapolating beyond families 5. Low prevalence in normal populations. While these criteria provide guidance, the need for clinical judgment when qualifying CNVs as pathogenic or benign becomes evident when looking at actual laboratory data as compared to literature reports. Accordingly, this chapter will supplement the listing of published CNVs from the literature [3] with those from 1210 consecutive microarray analyses from 2009 to 2014 at the Texas Tech Health Science Center Cytogenetic Laboratory (Tx, coordinated by author VST). Recurring literature CNVs with concurrent findings are recognized as syndromes, coupled with their appropriate six-digit number in parentheses when listed in Online Mendelian Inheritance Man [3]. © Springer Nature Singapore Pte Ltd. 2017 H.E. Wyandt et al., Human Chromosome Variation: Heteromorphism, Polymorphism and Pathogenesis, DOI 10.1007/978-981-10-3035-2_10
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A CNV Catalogue
Since aCGH has become the first line of chromosome testing [1, 2], CNVs large enough to be detected by routine chromosome analysis are included in the Tx database. Although the lower limit of aneuploid segment size detectable by microscopy is usually cited as 8–10 Mb, those of 25 Mb or larger were excluded for this survey. This number is based on the *22 Mb 5q14.3q21.3 Tx deletion (Fig. 1.2 and Chap. 9) that was detected by karyotype only after it was demonstrated by aCGH [4]. Removal of 59 CNVs larger than 25 Mb and 8 cases with a single large CNV left 1202 cases in the Tx database for this review; there were 51 cases where one or more CNVs over 25 Mb were the only pathogenic finding. Another arbitrary distinction was to interpret those Tx CNVs larger than 400 kb as likely pathogenic and those smaller as likely benign, listing them respectively in the upper or lo
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