Characterization by array-CGH of an interstitial de novo tandem 6p21.2p22.1 duplication in a boy with epilepsy and developmental delay

Andrieux, Joris; Richebourg, Steven; Duban‐Bedu, Bénédicte; Petit, Florence; Leprêtre, Frédéric; Sukno, Sylvie; Dehouck, Marie-Bertille; Delobel, Bruno

doi:10.1016/j.ejmg.2008.02.010

Cited by 10 publications

(11 citation statements)

References 8 publications

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“…The most significant interval (between SNPs rs1233399 and rs29225; top p = 3.4 × 10 -3 ) spans the 3' end of the GABBR1 (Gamma-aminobutyric acid (GABA) B receptor, 1) and the overlapping UBD (Ubiquitin D) loci. GABBR1 is highly expressed in nervous systems and has been suggested as a candidate region for neuropsychiatric disorders [45,46]. A recent study showed that the expression levels of GABBR1 are significantly lower in several brain regions in patients with autism compared with healthy controls [47].…”

Section: Resultsmentioning

confidence: 99%

Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia

et al. 2010

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BackgroundGenome-wide studies on autism spectrum disorders (ASDs) have mostly focused on large-scale population samples, but examination of rare variations in isolated populations may provide additional insights into the disease pathogenesis.MethodsAs a first step in the genetic analysis of ASD in Croatia, we characterized genetic variation in a sample of 103 subjects with ASD and 203 control individuals, who were genotyped using the Illumina HumanHap550 BeadChip. We analyzed the genetic diversity of the Croatian population and its relationship to other populations, the degree of relatedness via Runs of Homozygosity (ROHs), and the distribution of large (>500 Kb) copy number variations.ResultsCombining the Croatian cohort with several previously published populations in the FastME analysis (an alternative to Neighbor Joining) revealed that Croatian subjects cluster, as expected, with Southern Europeans; in addition, individuals from the same geographic region within Europe cluster together. Whereas Croatian subjects could be separated from a sample of healthy control subjects of European origin from North America, Croatian ASD cases and controls are well mixed. A comparison of runs of homozygosity indicated that the number and the median length of regions of homozygosity are higher for ASD subjects than for controls (p = 6 × 10-3). Furthermore, analysis of copy number variants found a higher frequency of large chromosomal rearrangements (>2 Mb) in ASD cases (5/103) than in ethnically matched control subjects (1/197, p = 0.019).ConclusionsOur findings illustrate the remarkable utility of high-density genotype data for subjects from a limited geographic area in dissecting genetic heterogeneity with respect to population and disease related variation.

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Section: Resultsmentioning

confidence: 99%

Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia

et al. 2010

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“…Interstitial direct tandem duplications causing a partial trisomy 6p are rare events. Since the first description by Villa et al [] of a patient with an interstitial tandem duplication of 6p, three more patients have been described [Ng et al, ; Andrieux et al, ; Bart et al, ]. Several other reported cases with pure trisomy 6p resulted from interchromosomal duplications or interchromosomal insertions.…”

Section: Discussionmentioning

confidence: 99%

“…After the Therkelsen's report of the first cases of partial trisomy 6p in 1971 [Therkelsen et al, ], several other cases of partial trisomy 6p have been described [Villa et al, ; Ng et al, ; Dominguez et al, ; Fogu et al, ; Andrieux et al, ; Bart et al, ]. Most of them derive from an imbalance of a familial reciprocal translocation, causing a “pure” duplication (without other imbalances) or a 6p duplication with a concomitant aneuploidy [Petkovic et al, ].…”

Section: Introductionmentioning

confidence: 99%

“…Most of them derive from an imbalance of a familial reciprocal translocation, causing a “pure” duplication (without other imbalances) or a 6p duplication with a concomitant aneuploidy [Petkovic et al, ]. Tandem intrachromosomal duplications are rare and all the cases described so far are de novo [Villa et al, ; Ng et al, ; Andrieux et al, ; Bart et al, ].…”

Section: Introductionmentioning

confidence: 99%

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Familial trisomy 6p in mother and daughter

Savarese

Grandone

Perone

et al. 2013

American J of Med Genetics Pt A

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Several patients with partial trisomy 6p resulting from parental balanced translocations or from a de novo duplication or insertion have already been described. Here, we report on the first case of familial pure trisomy 6p as a result of interstitial tandem duplication. The patient, an 11-year-old female, presented with mild dysmorphic features, moderate intellectual disability with behavioral disturbances, immunodeficiency, and epilepsy. Conventional cytogenetic analysis showed a duplication of the 6p region in the patient and in her mother presenting with a partially overlapping phenotype. The rearrangement was confirmed and defined by molecular cytogenetic analysis, including FISH and array CGH analysis showing a gain of ~13.8 Mb from 6p12.3 to 6p21.31. The phenotype of a pure partial trisomy 6p is extremely heterogeneous depending on the gene contents of the duplicated region. The clinical features of our patients have been compared with overlapping cases from the literature.

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“…Recently, a de novo interstitial tandem duplication of 6p22.1-p21.2 was detected by aCGH in a karyotypically normal boy with developmental delay [Andrieux et al, 2008]. Partial 6p duplications have been described as due to interstitial tandem duplications of 6p22.2-p21.1 [Ng et al, 2001] and 6p21.3-p12.3 [Villa et al, 2000], or interchromosomal insertions, such as (16; 6)(p12;p21.2-p23) [Dominguez et al, 2003].…”

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confidence: 99%

Analysis of Segmental Duplications, Mouse Genome Synteny and Recurrent Cancer-Associated Amplicons in Human Chromosome 6p21–p12

Martin

Yoshimoto²,

Ludkovski³

et al. 2010

Cytogenet Genome Res

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It has been proposed that regions of microhomology in the human genome could facilitate genomic rearrangements, copy number transitions, and rapid genomic change during tumor progression. To investigate this idea, this study examines the role of repetitive sequence elements, and corresponding syntenic mouse genomic features, in targeting cancer-associated genomic instability of specific regions of the human genome. Automated database-mining algorithms designed to search for frequent copy number transitions and genomic breakpoints were applied to 2 publicly-available online databases and revealed that 6p21–p12 is one of the regions of the human genome most frequently involved in tumor-specific alterations. In these analyses, 6p21–p12 exhibited the highest frequency of genomic amplification in osteosarcomas. Analysis of repetitive elements in regions of homology between human chromosome 6p and the syntenic regions of the mouse genome revealed a strong association between the location of segmental duplications greater than 5 kilobase-pairs and the position of discontinuities at the end of the syntenic region. The presence of clusters of segmental duplications flanking these syntenic regions also correlated with a high frequency of amplification and genomic alteration. Collectively, the experimental findings, in silico analyses, and comparative genomic studies presented here suggest that segmental duplications may facilitate cancer-associated copy number transitions and rearrangements at chromosome 6p21–p12. This process may involve homology-dependent DNA recombination and/or repair, which may also contribute towards the overall plasticity of the human genome.

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Characterization by array-CGH of an interstitial de novo tandem 6p21.2p22.1 duplication in a boy with epilepsy and developmental delay

Cited by 10 publications

References 8 publications

Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia

Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia

Familial trisomy 6p in mother and daughter

Analysis of Segmental Duplications, Mouse Genome Synteny and Recurrent Cancer-Associated Amplicons in Human Chromosome 6p21–p12

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