Microduplications in 22q11.2 and 8q22.1 associated with mild mental retardation and generalized overgrowth

Tarsitano, Marina; Ceglia, Carlo; Novelli, Antonio; Capalbo, Anna; Lombardo, Barbara; Pastore, Lucio; G, Fioretti; Vicari, Laura; Pisanti, Maria Antonietta; Friso, Patrizia; Cavaliere, Maria Luigia

doi:10.1016/j.gene.2013.11.051

Cited by 24 publications

(23 citation statements)

References 17 publications

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“…We found 2 overlapping deletions (case 266246 and 300526), both maternally transmitted, in TOP3B (MIM#603582), a gene previously reported with a duplication in a patient with mild ID and generalized overgrowth . Subject 266246 inherited the deletion from the unaffected mother.…”

Section: Resultsmentioning

confidence: 74%

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes

et al. 2017

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Section: Resultsmentioning

confidence: 74%

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes

et al. 2017

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“…Consistent with this notion, copy number variants of both Top3β and TDRD3 have been reported in individuals with autism spectrum disorders (listed in http://autismkb.cbi.pku.edu.cn). Micro-duplication of the genomic region containing Top3β gene has also been reported for a patient with mental retardation (30). Future studies are needed to identify genes regulated by the Top3β–TDRD3 complex, which could provide targets for therapeutic intervention.…”

Section: Discussionmentioning

confidence: 86%

Topoisomerase 3β is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction

Ahmad

Shen

et al. 2016

Nucleic Acids Res

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Human cells contain five topoisomerases in the nucleus and cytoplasm, but which one is the major topoisomerase for mRNAs is unclear. To date, Top3β is the only known topoisomerase that possesses RNA topoisomerase activity, binds mRNA translation machinery and interacts with an RNA-binding protein, FMRP, to promote synapse formation; and Top3β gene deletion has been linked to schizophrenia. Here, we show that Top3β is also the most abundant mRNA-binding topoisomerase in cells. Top3β, but not other topoisomerases, contains a distinctive RNA-binding domain; and deletion of this domain diminishes the amount of Top3β that associates with mRNAs, indicating that Top3β is specifically targeted to mRNAs by its RNA binding domain. Moreover, Top3β mutants lacking either its RNA-binding domain or catalytic residue fail to promote synapse formation, suggesting that Top3β requires both its mRNA-binding and catalytic activity to facilitate neurodevelopment. Notably, Top3β proteins bearing point mutations from schizophrenia and autism individuals are defective in association with FMRP; whereas one of the mutants is also deficient in binding mRNAs, catalyzing RNA topoisomerase reaction, and promoting synapse formation. Our data suggest that Top3β is the major topoisomerase for mRNAs, and requires both RNA binding and catalytic activity to promote neurodevelopment and prevent mental dysfunction.

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“…Recently, a microduplication of 22q11.2 syndrome was identified and associated with DiGeorge/Velocardiofacial syndrome (DGS/VCFS). The 22q11.2 region is susceptible to chromosomal rearrangements (Brunet et al, 2006), and the clinical characteristics of partial microduplication of 22q syndrome have been described as extremely variable, ranging from mild learning disabilities to severe congenital malformations (Portnoï et al, 2005;Tarsitano et al, 2014). Typically, the phenotype of microduplication of 22q11.2 syndrome includes intellectual disability, heart defects, urogenital abnormalities, velopharyngeal insufficiency, down-slanting palpebral fissures, telecanthus, long narrow face, and nasal speech.…”

Section: Discussionmentioning

confidence: 99%

A rare case of trisomy 11q23.3-11q25 and trisomy 22q11.1-22q11.21

Ps¹,

Hf²,

Chen³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Partial duplication of the long arm of chromosome 11 and the partial trisomy of 22q are uncommon karyotypic abnormalities. Here, we report the case of a 6-year-old girl who showed partial trisomy of 11q and 22q, as a result of a maternal balanced reciprocal translocation (11;22), and exhibited dysmorphic features, severe intellectual disability, brain malformations, and speech delay related to this unique chromosomal abnormality. Array comparative genomic hybridization (array CGH) revealed a gain in copy number on the long arm of chromosome 11, spanning at least 18.22 Mb. Additionally, there was a gain in copy number on the long arm of chromosome 22, spanning at least 3.46 Mb. FISH analysis using a chromosome 11 short arm telomere probe (11p14.2), a chromosome 11 long arm telomere probe (11q24.3), and a chromosome 22 long arm telomere probe (22q13.33) confirmed the origin of the marker chromosome. It has been confirmed by the State Key Laboratory of Medical Genetics of China that this is the first reported instance of the karyotype 47,XX, +der (22

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Microduplications in 22q11.2 and 8q22.1 associated with mild mental retardation and generalized overgrowth

Cited by 24 publications

References 17 publications

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes

Topoisomerase 3β is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction

A rare case of trisomy 11q23.3-11q25 and trisomy 22q11.1-22q11.21

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