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

Details

Serval ID
serval:BIB_37F48FE8E1F9
Type
Article: article from journal or magazin.
Collection
Publications
Title
Inactivation of AMMECR1 is associated with growth, bone, and heart alterations.
Journal
Human mutation
Author(s)
Moysés-Oliveira M., Giannuzzi G., Fish R.J., Rosenfeld J.A., Petit F., Soares M.F., Kulikowski L.D., Di-Battista A., Zamariolli M., Xia F., Liehr T., Kosyakova N., Carvalheira G., Parker M., Seaby E.G., Ennis S., Gilbert R.D., Hagelstrom R.T., Cremona M.L., Li W.L., Malhotra A., Chandrasekhar A., Perry D.L., Taft R.J., McCarrier J., Basel D.G., Andrieux J., Stumpp T., Antunes F., Pereira G.J., Neerman-Arbez M., Meloni V.A., Drummond-Borg M., Melaragno M.I., Reymond A.
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Publication state
Published
Issued date
02/2018
Peer-reviewed
Oui
Volume
39
Number
2
Pages
281-291
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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
Animals, Blotting, Western, Bone and Bones/metabolism, Bone and Bones/physiology, Cell Cycle/genetics, Cell Cycle/physiology, Cell Line, Exome/genetics, Female, HeLa Cells, Heart/physiology, Humans, Male, Proteins/genetics, Whole Genome Sequencing, Zebrafish, AMMECR1, X-linked disease, bone dysplasia, growth delay, heart alteration
Pubmed
Web of science
Create date
07/12/2017 22:23
Last modification date
20/08/2019 14:26
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