Inactivation of AMMECR1 is associated with growth, bone, and heart alterations

Inactivation of AMMECR1 is associated with growth, bone, and heart alterations

Author Moyses-Oliveira, Mariana Autor UNIFESP Google Scholar
Giannuzzi, Giuliana Google Scholar
Fish, Richard J. Google Scholar
Rosenfeld, Jill A. Google Scholar
Petit, Florence Google Scholar
Soares, Maria de Fatima Autor UNIFESP Google Scholar
Kulikowski, Leslie Domenici Google Scholar
Di-Battista, Adriana Autor UNIFESP Google Scholar
Zamariolli, Malu Autor UNIFESP Google Scholar
Xia, Fan Google Scholar
Liehr, Thomas Google Scholar
Kosyakova, Nadezda Google Scholar
Carvalheira, Gianna Autor UNIFESP Google Scholar
Parker, Michael Google Scholar
Seaby, Eleanor G. Google Scholar
Ennis, Sarah Google Scholar
Gilbert, Rodney D. Google Scholar
Hagelstrom, R. Tanner Google Scholar
Cremona, Maria L. Google Scholar
Li, Wenhui L. Google Scholar
Malhotra, Alka Google Scholar
Chandrasekhar, Anjana Google Scholar
Perry, Denise L. Google Scholar
Taft, Ryan J. Google Scholar
McCarrier, Julie Google Scholar
Basel, Donald G. Google Scholar
Andrieux, Joris Google Scholar
Stumpp, Taiza Google Scholar
Antunes, Fernanda Autor UNIFESP Google Scholar
Pereira, Gustavo Jose Autor UNIFESP Google Scholar
Neerman-Arbez, Marguerite Google Scholar
Meloni, Vera Ayres Autor UNIFESP Google Scholar
Drummond-Borg, Margaret Google Scholar
Melaragno, Maria Isabel Autor UNIFESP Google Scholar
Reymond, Alexandre Google Scholar
Abstract We report five individuals with loss-of-function of the X-linked AMMECR1: a girl with a balanced X-autosome translocation and inactivation of the normal X-chromosome

two boys with maternally inherited and de novo nonsense variants

and two half-brothers with maternally inherited microdeletion variants. They present with short stature, cardiac and skeletal abnormalities, and hearing loss. Variants of unknown significance in AMMECR1 in four male patients from two families with partially overlapping phenotypes were previously reported. AMMECR1 is coexpressed with genes implicated in cell cycle regulation, five of which were previously associated with growth and bone alterations. Our knockdown of the zebrafish orthologous gene resulted in phenotypes reminiscent of patients' features. The increased transcript and encoded protein levels of AMMECR1L, an AMMECR1 paralog, in the t(X;9) patient's cells indicate a possible partial compensatory mechanism. AMMECR1 and AMMECR1L proteins dimerize and localize to the nucleus as suggested by their nucleic acid-binding RAGNYA folds. Our results suggest that AMMECR1 is potentially involved in cell cycle control and linked to a new syndrome with growth, bone, heart, and kidney alterations with or without elliptocytosis.
Keywords AMMECR1
bone dysplasia
growth delay
heart alteration
X-linked disease
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
Faculty of Biology and Medicine, University of Lausanne
Swiss National Science Foundation
Lithuanian-Swiss Cooperation Program
Grant number FAPESP: 2014/11572-8
Swiss National Science Foundation 31003A_160203
Date 2018
Published in Human Mutation. Hoboken, v. 39, n. 2, p. 281-291, 2018.
ISSN 1059-7794 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 281-291
Origin http://dx.doi.org/10.1002/humu.23373
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000419711500011
URI https://repositorio.unifesp.br/handle/11600/54235

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