Array-CGH analysis using 244k Agilent oligoarray revealed a de novo 17q21.31 microduplication in a 10-year-old girl with severe psychomotor developmental delay, facial dysmorphism, microcephaly, abnormal digits and hirsutism. The duplication encompassed the MAPT and CRHR1 genes and was reciprocal to the recently described 17q21.31 microdeletion, associated with a recognizable clinical phenotype. Genotyping showed that the duplication was derived from non-allelic homologous recombination of paternal H1 and H2 haplotypes. To our knowledge this is the first report of a patient with a 17q21.31 microduplication.
"microduplications have been seen less frequently . A recent study  reported the frequency among live births of 1/55,000 and 1/327,000 for microdeletions and microduplications, respectively, which suggests a ratio of 6 : 1, which is lower than expected of NAHR . Importantly, these ratios should be viewed against the molecular background in which they occur and the genomic region being investigated in that the H2 inversion haplotype is expected to favour microdeletions as opposed to microduplications . "
[Show abstract][Hide abstract] ABSTRACT: Concurrent cryptic microdeletion and microduplication syndromes have recently started to reveal themselves with the advent of microarray technology. Analysis has shown that low-copy repeats (LCRs) have allowed chromosome regions throughout the genome to become hotspots for nonallelic homologous recombination to take place. Here, we report a case of a 7.5-year-old girl who manifests microcephaly, developmental delay, and mild dysmorphic features. Microarray analysis identified a microduplication in chromosome 17q21.31, which encompasses the CRHR1, MAPT, and KANSL1 genes, as well as a microdeletion in chromosome 7q31.33 that is localised within the GRM8 gene. To our knowledge this is one of only a few cases of 17q21.31 microduplication. The clinical phenotype of patients with this microduplication is milder than of those carrying the reciprocal microdeletions, and suggests that the lower incidence of the former compared to the latter may be due to underascertainment.
"deletion and 1 case with duplication , with cases 1 and 4 also having one additional aberration each. The phenotypic characteristics of our patients are presented in Table 1 and are in their majority similar to those reported, although cases 1 and 4 are more severely affected than those published (Shaw-Smith et al., 2006; Kirchhoff et al., 2007; Koolen et al., 2008; Grisart et al., 2009; Tan et al., 2009; Dubourg et al., 2010) (Table 2), probably due to the additional microdeletions: maternally inherited Xq21.31 and the de novo 15q11.2 respectively. "
[Show abstract][Hide abstract] ABSTRACT: The recognition of the 17q21.31 microdeletion and microduplication syndrome has been facilitated by high resolution oligonucleotide array comparative genome hybridization technology (aCGH). Molecular analysis of the 17q21.31 microdeletion/duplication syndrome demonstrated a critical region involving at least six genes, including STH and MAPT. The 17q21.31 microdeletion syndrome has an incidence of 1 in 16,000 births, while the microduplication 17q21.31 has been reported so far in only five patients. In general, phenotypes associated with 17q21.31 microduplication seem to be milder than those associated with the microdeletion. Here, we present four patients who have been referred for genetic evaluation by clinical geneticists due to developmental delay and minor congenital abnormalities. Previous standard karyotypes were negative, while aCGH analysis revealed three patients with 17q21.31 microdeletion and one with the respective microduplication, being the sixth reported case so far. Most importantly one of the microdeletion cases involves only partial MAPT gene deletion while leaving the STH gene intact. Two of our patients, one with the 17q21.31 microdeletion and another with the respective microduplication, carried additional clinically relevant microdeletions (del Xq21.31 and del 15q11.2, respectively), possibly modifying their phenotype.
"deletion (Smith–Magenis syndrome) and duplication (Potocki–Lupski syndrome) (Bi et al. 2003; Potocki et al. 2007), and 17q21.31 deletion and duplication (Kirchhoff et al. 2007; Koolen et al. 2006; Sharp et al. 2006 ; Shaw - Smith et al. 2006 ) . Recently, a number of non - recurrent rearrangements have been shown also to result from genomic architectural features that may stimulate their formation through the proposed fork stalling and template switching ( FoSTeS ) / microhomology - mediated break - induced replication ( MMBIR ) mechanism ( Lee et al. 2007 ) , e . "
[Show abstract][Hide abstract] ABSTRACT: We report four new patients with a submicroscopic deletion in 15q24 manifesting developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, and characteristic facial features. These clinical features are shared with six recently reported patients with a 15q24 microdeletion, supporting the notion that this is a recognizable syndrome. We describe a case of an ~2.6 Mb microduplication involving a portion of the minimal deletion critical region in a 15-year-old male with short stature, mild mental retardation, attention deficit hyperactivity disorder, Asperger syndrome, decreased joint mobility, digital abnormalities, and characteristic facial features. Some of these features are shared with a recently reported case with a 15q24 microduplication involving the minimal deletion critical region. We also report two siblings and their mother with duplication adjacent and distal to this region exhibiting mild developmental delay, hypotonia, tapering fingers, characteristic facial features, and prominent ears. The deletion and duplication breakpoints were mapped by array comparative genomic hybridization and the genomic structure in 15q24 was analyzed further. Surprisingly, in addition to the previously recognized three low-copy repeat clusters (BP1, BP2, and BP3), we identified two other paralogous low-copy repeat clusters that likely mediated the formation of alternative sized 15q24 genomic rearrangements via non-allelic homologous recombination.
Human Genetics 07/2009; 126(4):589-602. DOI:10.1007/s00439-009-0706-x · 4.82 Impact Factor
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