Molecular Cytogenetic Characterization of Two Cases with de novo Small Mosaic Supernumerary Marker Chromosomes Derived from Chromosome 16: Towards a Genotype/Phenotype Correlation

Melo, Joana B.; Matoso, Eunice; Polityko, A; Saraiva, Jorge; Backx, Liesbeth; Vermeesch, Joris Robert; Kosyakova, Nadezda; Ewers, Elisabeth; Liehr, Thomas; Carreira, Isabel M.

doi:10.1159/000227834

Cited by 5 publications

(6 citation statements)

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“…Herein, we report a series of 39 de novo sSMC detected among 65,000 prenatal samples. This is the largest series of prenatally diagnosed and molecularly characterized sSMC, the other reports being limited to unique cases or specific chromosomes (24)(25)(26)(27)(28)(29). The characterization of sSMC by array-CGH or SNP array makes it possible to determine the chromosome involved, the presence of euchromatin, the size of the euchromatin material and the number of genes involved, and provides clues for more pertinent genetic counselling.…”

Section: Discussionmentioning

confidence: 99%

“…Array-CGH and SNP array are powerful tools for delineating chromosomal imbalances. However, there have been no large series reporting the application of this technology to sSMC in a postnatal (14)(15)(16)(17)(18)(19)(20)(21)(22) or prenatal context (23)(24)(25)(26)(27)(28)(29), or both (30,31). Genotype-phenotype correlations should be extended, and SNP array also offers the possibility to detect uniparental disomy (UPD), in particular, for sSMC derived from chromosome 6, 7, 11 and 20 (32,33).…”

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confidence: 99%

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Molecular characterization of 39 de novosSMC: contribution to prognosis and genetic counselling, a prospective study

et al. 2013

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Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Molecular characterization of 39 de novosSMC: contribution to prognosis and genetic counselling, a prospective study

et al. 2013

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“…We report a child with mild‐to‐moderate intellectual disability, microcephaly, language dyspraxia, developmental delay, mild dysmorphism, and cerebellar cortical dysplasia who has a gain of chromosome 16q11.2–16q12.1 later found to be a de novo mosaic marker chromosome 16. sSMCs are structurally abnormal chromosomes that cannot be thoroughly characterized by conventional banding cytogenetics. sSMC derived from chromosome 16 are rare and so far it is not clear which regions of the chromosome are critical and have clinical consequences [Melo et al, 2009].…”

Section: Discussionmentioning

confidence: 99%

Mosaic marker chromosome 16 resulting in 16q11.2–q12.1 gain in a child with intellectual disability, microcephaly, and cerebellar cortical dysplasia

Zerem¹,

Vinkler²,

Michelson³

et al. 2011

American J of Med Genetics Pt A

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Proximal duplications of the long arm of chromosome 16 are rare and only a few patients have been reported. Clinically, the patients do not have a distinctive syndromic appearance; however they all show some degree of intellectual disability and most have severely delayed speech development. We report on a child presenting with mild-to-moderate intellectual disability, microcephaly, language dyspraxia, and mild dysmorphisms who was found to have a mosaic gain of chromosome 16q (16q11.2-16q12.1). Magnetic resonance imaging done at the age of 4 years demonstrated cerebellar cortical dysplasia involving the vermis and hemispheres. This is the first report of cerebellar anomalies in a patient with partial trisomy 16q. The genes ZNF423 and CBLN1 found in the duplicated region play a role in the development of the cerebellum and may be responsible for the cerebellar cortical dysplasia.

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“…Except for some small modifications, probe preparation, preblocking, and hybridization and scanning of the slide were performed as described previously (Fiegler et al 2003;Vermeesch et al 2005;Melo et al 2009). A full tiling BAC array specific for chromosome 5 was used, with a resolution of 100-150 Kb (VIB MicroArrays Facility; http://www.microarrays.be).…”

Section: Fish Studiesmentioning

confidence: 99%

Chromosome 5 derived small supernumerary marker: towards a genotype/phenotype correlation of proximal chromosome 5 imbalances

et al. 2011

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Small supernumerary marker chromosomes (sSMC) are a morphological heterogeneous group of additional abnormal chromosomes that cannot be characterized alone by conventional banding cytogenetics. Molecular cytogenetic techniques are valuable tools for the accurate identification of sSMC and a prerequisite for sound genetic counseling based on refined genotype/phenotype correlation. We describe a new case of a retarded patient with an sSMC derived from chromosome 5. The characterization of the sSMC was done by subcentromere-specific multicolor (subcenM) fluorescence in-situ hybridization (FISH) and by full tilling resolution array analysis, after microdissection and amplification of the marker DNA. Uniparental disomy for normal sister chromosomes of the sSMC(5) was excluded. The karyotype was mos47,XX,+r(5)(::p11.1 → q12.1::)[70%]/46,XX[30%], being the trisomic region between 46.15 ∼ 49.56 Mb and 61.25 ∼ 61.335 Mb, a region known to harbor ∼45 annotated genes. Together with a review of the previously described cases of sSMC(5) and duplications involving the 5q proximal region, we can conclude that trisomy of the 5q11 region is associated with learning difficulties and speech delay.

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Molecular Cytogenetic Characterization of Two Cases with de novo Small Mosaic Supernumerary Marker Chromosomes Derived from Chromosome 16: Towards a Genotype/Phenotype Correlation

Cited by 5 publications

References 51 publications

Molecular characterization of 39 de novosSMC: contribution to prognosis and genetic counselling, a prospective study

Molecular characterization of 39 de novosSMC: contribution to prognosis and genetic counselling, a prospective study

Mosaic marker chromosome 16 resulting in 16q11.2–q12.1 gain in a child with intellectual disability, microcephaly, and cerebellar cortical dysplasia

Chromosome 5 derived small supernumerary marker: towards a genotype/phenotype correlation of proximal chromosome 5 imbalances

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