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Identification of a 21q22 duplication in a Silver–Russell syndrome patient further narrows down the Down syndrome critical region
Author(s) -
Eggermann Thomas,
Schönherr Nadine,
Spengler Sabrina,
Jäger Susanne,
Denecke Bernd,
Binder Gerhard,
Baudis Michael
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33217
Subject(s) - gene duplication , genetics , biology , gene , chromosome 21 , down syndrome , phenotype , chromosome
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 β‐subunit of the KvLQT1 channel as the slow component of the cardiac delayed rectifier K + current. Since duplication of the KCNQ1 gene encoding the α‐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. © 2010 Wiley‐Liss, Inc.