Common Recurrent Microduplication Syndromes: Diagnosis and Management in Clinical Practice
ABSTRACT Details on the phenotypic consequences of genomic microdeletions and microduplications are rapidly emerging in the wake of increased utilization of high-resolution methods for the detection of genomic copy number variants (CNVs). Due to their recent discovery, the complete phenotypic characterization of these syndromes is still in progress. For practicing clinicians, this unprecedented molecular diagnostic capability has in many cases outpaced our ability to convey conclusive information regarding these conditions to patients and family members. In particular, genomic microduplication syndromes are frequently associated with variable phenotypes and incomplete penetrance, leading to difficulty in counseling regarding the potential future consequences of a given microduplication. In this review, we have attempted to provide an initial set of recommendations for the management of patients with recurrent microduplication syndromes. We summarize the clinical information for microduplications of 14 different genomic regions and provide a framework for clinical evaluation and anticipatory guidance in these conditions. It is our expectation that these preliminary guidelines will be revised further for each microduplication syndrome as more information becomes available.
- SourceAvailable from: Paul R Fisher
Protein Structure, 04/2012; , ISBN: 978-953-51-0555-8
- "The main method for predicting the function of a gene product in the absence of experimental data is termed 'homology-based transfer' (Friedberg, 2006; Sleator & Walsh, 2010). This approach is based on the detection of significant amino acid sequence similarity to a protein(s) of known function using programmes such as BLAST (Altschul et al., 1997). "
- "The main method for predicting the function of a gene product in the absence of experimental data is termed 'homologybased transfer' (Friedberg, 2006; Sleator & Walsh, 2010). This approach is based on the detection of significant amino acid sequence similarity to a protein(s) of known function using programmes such as BLAST (Altschul et al., 1997). "
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ABSTRACT: The aims of this study were to create a copy number variant (CNV) profile of human chromosome 22 and to establish a genotype-phenotype correlation for patients with genomic abnormalities on chromosome 22. Thus, 1,654 consecutive pediatric patients with a diversity of clinical findings were evaluated by high-resolution chromosomal microarray analysis (CMA). We identified 25 individuals with abnormal CNVs on chromosome 22, representing 1.5% of the cases analyzed in this cohort. Meanwhile, we detected 1,298 benign CNVs on this chromosome in these individuals. Twenty-one of the 25 abnormal CNVs and the majority of the benign CNVs occurred through involvement of the 8 unstable genomic regions enriched with low copy repeats (LCR22A-H). The highly dynamic status of LCR22s within the 22q11 region facilitates the formation of diverse genomic abnormalities. This CNV profile provides a general perspective of the spectrum of chromosome 22 genomic imbalances and subsequently improves the CNV-phenotype correlations.Cytogenetic and Genome Research 01/2011; 134(4):260-8. DOI:10.1159/000330123 · 1.91 Impact Factor