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| Some of these aberrations are apparently benign CNVs and are usually inherited from a parent (Lee 2007). If identical alterations are found either in one of the unaffected parents, or in independent normal controls, they most probably have no direct phenotypic
consequences; however, low penetrance and variable expressivity of the phenotype may complicate the analysis and genetic counseling. Currently, the publicly available CNV databases assist in making decisions about the clinical significance of imbalances detected by microarrays. Examples of such databases are the Database of Genomic Variants (http://projects.tcag.ca/variation). When determined as de novo in origin genomic imbalances are considered more likely pathological (Tyson 2005). This can be further supported if the implicated region contains gene(s) with functions compatible with the abnormal clinical findings or previously described patients with a similar genomic imbalance and a similar phenotype. The de novo occurrence of copy number alteration is, however, not an absolute evidence of its pathogenicity and caution must be exercised for possible non paternity. 40. Lee JA, Carvalho CM, Lupski JR. A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders. Cell. 2007 Dec 28;131(7):1235-47. 41. Lee, C., Iafrate A.J., and Brothman A.R., Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat Genet, 2007. 39(7 Suppl): p. S48-54. 79. Tyson C, et al. Submicroscopic deletions and duplications in individuals with intellectual disability detected by array-CGH. Am J Med Genet A. 2005 Dec 15;139(3):173-85. |
are apparently benign CNVs and are usually inherited from a parent [10]. If identical alterations are found either in one of the unaffected parents, or in independent normal controls, they most probably have no direct phenotypic consequences; however, low penetrance and variable expressivity of the phenotype may complicate the analysis and genetic counseling. Currently, the publicly available CNV databases assist in making decisions about the clinical significance of imbalances detected by microarrays. Examples of such databases are the Database of Genomic Variants (http://www.projects.tcag.ca/variation/, http://www.genome.ucsc.edu/ and http://www.sanger.ac.uk/PostGenomics/decipher/). Investigations of the parents and additional family members may often be necessary to interpret and clarify these results. The elimination of such regions from the new generations of microarray can improve the specificity and subsequently facilitate the genetic counseling.
When determined as de novo in origin genomic imbalances are considered pathogenic. This can be further supported if the implicated region contains gene(s) with functions compatible with the abnormal clinical findings or previously described patients with a similar genomic imbalance and a similar phenotype. The de novo occurrence of copy number alteration is, however, not an absolute evidence of its pathogenicity and caution must be exercised for possible nonpaternity. 10 Lee, C. et al. (2007) Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat. Genet. 39, S48–54 |
Nothing has been marked as a citation. The source is not given. "(Lee 2007)" cannot be uniquely resolved by the references given by Mmu. |
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