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Identification of a 21q22 duplication in a Silver-Russell syndrome patient further narrows down the Down syndrome critical region


Eggermann, T; Schönherr, N; Spengler, S; Jäger, S; Denecke, B; Binder, G; Baudis, M (2010). Identification of a 21q22 duplication in a Silver-Russell syndrome patient further narrows down the Down syndrome critical region. American Journal of Medical Genetics. Part A, 152A(2):356-359.

Abstract

Several duplications of chromosome 21q helped to narrow down the Down syndrome (DS) critical region (DSCR) to chromosomal band 21q22 with an approximate length of 5.4 Mb. Recently, it has been suggested that the facial gestalt of DS has been linked to the distal part of the DSCR whereas the proximal region harboring DSCR1/RCAN and DSCAM should be associated with the cardiac abnormalities. Here, we report on a patient with Silver-Russell syndrome (SRS) and a paternally inherited 0.46 Mb duplication in 21q22 affecting the KCNE1 and DSCR1/RCAN genes. The identification of an involvement of KCNE1 was interesting because it encodes the beta-subunit of the KvLQT1 channel as the slow component of the cardiac delayed rectifier K(+) current. Since duplication of the KCNQ1 gene encoding the alpha-subunit of the same channel was reported recently in another SRS patient, we screened both genes for mutations in a cohort of SRS patients without detecting pathologic variants. We presume that the duplication of the two functionally linked genes in different patients with the same disorder is a coincidental finding. However, the lack of DS typical clinical features in our case allows us to further narrow down the DSCR in 21q22. We conclude that DSCR1/RCAN is not sufficient for generating phenotypic features associated with DS but our observation does not contradict a possible role for DSCR1/RCAN in mediating DYRK1A-based effects. (c) 2010 Wiley-Liss, Inc.

Several duplications of chromosome 21q helped to narrow down the Down syndrome (DS) critical region (DSCR) to chromosomal band 21q22 with an approximate length of 5.4 Mb. Recently, it has been suggested that the facial gestalt of DS has been linked to the distal part of the DSCR whereas the proximal region harboring DSCR1/RCAN and DSCAM should be associated with the cardiac abnormalities. Here, we report on a patient with Silver-Russell syndrome (SRS) and a paternally inherited 0.46 Mb duplication in 21q22 affecting the KCNE1 and DSCR1/RCAN genes. The identification of an involvement of KCNE1 was interesting because it encodes the beta-subunit of the KvLQT1 channel as the slow component of the cardiac delayed rectifier K(+) current. Since duplication of the KCNQ1 gene encoding the alpha-subunit of the same channel was reported recently in another SRS patient, we screened both genes for mutations in a cohort of SRS patients without detecting pathologic variants. We presume that the duplication of the two functionally linked genes in different patients with the same disorder is a coincidental finding. However, the lack of DS typical clinical features in our case allows us to further narrow down the DSCR in 21q22. We conclude that DSCR1/RCAN is not sufficient for generating phenotypic features associated with DS but our observation does not contradict a possible role for DSCR1/RCAN in mediating DYRK1A-based effects. (c) 2010 Wiley-Liss, Inc.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:08 University Research Priority Programs > Systems Biology / Functional Genomics
07 Faculty of Science > Institute of Molecular Life Sciences
04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Date:25 January 2010
Deposited On:29 Jan 2010 13:53
Last Modified:05 Apr 2016 13:49
Publisher:Wiley-Blackwell
ISSN:1552-4825
Publisher DOI:10.1002/ajmg.a.33217
PubMed ID:20101688
Permanent URL: http://doi.org/10.5167/uzh-28716

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