Partial trisomy of chromosome 21 without the Down syndrome phenotype

Su, Mei Tsz; Kuan, Long Ching; Chou, Yen Yin; Tan, Shang Yi; Kuo, Tsung-Cheng; Kuo, Pao Lin

doi:10.1002/pd.4796

Cited by 8 publications

(11 citation statements)

References 13 publications

(38 reference statements)

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“…Recently, a report was published in which a partial 21q duplication did not show an obvious abnormal phenotype. The duplicated region resembled our case . It is difficult to say what the exact phenotype in our case would have been as the pregnancy was terminated.…”

mentioning

confidence: 60%

A prenatal case of partial trisomy 21 (q22.2q22.3), resulting from a paternal insertion translocation ins(16;21) and uncovered by QF‐PCR, and characterized by array CGH and FISH

Bhola

Nieuwint

Stuurman

2018

Clinical Case Reports

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mentioning

confidence: 60%

A prenatal case of partial trisomy 21 (q22.2q22.3), resulting from a paternal insertion translocation ins(16;21) and uncovered by QF‐PCR, and characterized by array CGH and FISH

Bhola

Nieuwint

Stuurman

2018

Clinical Case Reports

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“…While this work was in revision, two additional PT21 cases were reported (13) in two Taiwanese fetuses without DS, who both inherited from their respective healthy mothers a proximal (14.3 Mb at 21q11.2q21.3) and a distal (4.4 Mb on 21q22.2q22.3) duplication, respectively. These two cases alone allow the confirmation that duplication of regions covering a total of 55% of 21q, and not including 21q22.13 where we locate HR-DSCR, is not associated to DS.…”

Section: Discussionmentioning

confidence: 93%

“…However, only a few cases are at present useful in this respect; for example, two subjects with PT21 in absence of APP duplication did not develop AD until at least 65 (38) or 78 (81,82) years of age (our cases #111 and #77, respectively). Articles about PT21 cases are typically not prospectively followed by successive reports about the onset or not of AD, although the potential relevance of a similar observation is clear; for example, the just published report by Su et al (13) states that ‘whether these two probands have CBS - or APP -associated disorders is an issue that remains to be closely followed up in their later lives’.…”

Section: Discussionmentioning

confidence: 99%

“…The third article (13) has been cited and discussed in the Introduction and Discussion sections above.…”

Section: Methodsmentioning

confidence: 99%

“…As a recent remarkable example (12), a terminal duplication of at least 5 Mb on distal 21q22.3 including 77 protein-coding genes (30% of all protein-coding Hsa21 genes) was not related to an abnormal phenotype (Hsa21 interval 41.6–46.6 Mb on GenBank sequence NC_000021.9; all chromosomal coordinates are adjusted in this work to the current Genome Reference Consortium (GRC) human genome assembly GRCh38, or hg38, December 2013). Similarly, while this work was in revision, a new case of a 4.4 Mb interstitial duplication on 21q22.2q22.3 (39 612 165–43 981 027 interval in hg38), including 51 genes of which 7 are in the Online Mendelian Inheritance in Man (OMIM) Genetic Morbid Map, was reported both in a mother with a completely normal clinical picture and her female fetus with no dysmorphism and normal psycho-motor development at two years of age (13). In addition, overexpression of one gene might compensate overexpression of another gene present in the duplicated chromosome (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype

et al. 2016

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A ‘Down Syndrome critical region’ (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6–8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS.

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Partial trisomy 21 map: Ten cases further supporting the highly restricted Down syndrome critical region (HR‐DSCR) on human chromosome 21

Pelleri

Cicchini

Petersen

et al. 2019

Molec Gen & Gen Med

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Background Down syndrome (DS) is characterized by the presence of an extra full or partial human chromosome 21 (Hsa21). An invaluable model to define genotype‐phenotype correlations in DS is the study of the extremely rare cases of partial (segmental) trisomy 21 (PT21), the duplication of only a delimited region of Hsa21 associated or not to DS. A systematic retrospective reanalysis of 125 PT21 cases described up to 2015 allowed the creation of the most comprehensive PT21 map and the identification of a 34‐kb highly restricted DS critical region (HR‐DSCR) as the minimal region whose duplication is shared by all PT21 subjects diagnosed with DS. We reanalyzed at higher resolution three cases previously published and we accurately searched for any new PT21 reports in order to verify whether HR‐DSCR limits could prospectively be confirmed and possibly refined. Methods Hsa21 partial duplications of three PT21 subjects were refined by adding array‐based comparative genomic hybridization data. Seven newly described PT21 cases fulfilling stringent cytogenetic and clinical criteria have been incorporated into the PT21 integrated map. Results The PT21 map now integrates fine structure of Hsa21 sequence intervals of 132 subjects onto a common framework fully consistent with the presence of a duplicated HR‐DSCR, on distal 21q22.13 sub‐band, only in DS subjects and not in non‐DS individuals. No documented exception to the HR‐DSCR model was found. Conclusions The findings presented here further support the association of the HR‐DSCR with the diagnosis of DS, representing an unbiased validation of the original model. Further studies are needed to identify and characterize genetic determinants presumably located in the HR‐DSCR and functionally associated to the critical manifestations of DS.

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Partial trisomy of chromosome 21 without the Down syndrome phenotype

Cited by 8 publications

References 13 publications

A prenatal case of partial trisomy 21 (q22.2q22.3), resulting from a paternal insertion translocation ins(16;21) and uncovered by QF‐PCR, and characterized by array CGH and FISH

A prenatal case of partial trisomy 21 (q22.2q22.3), resulting from a paternal insertion translocation ins(16;21) and uncovered by QF‐PCR, and characterized by array CGH and FISH

Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype

Partial trisomy 21 map: Ten cases further supporting the highly restricted Down syndrome critical region (HR‐DSCR) on human chromosome 21

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