PUBLICATION
Inactivation of AMMECR1 is associated with growth, bone and heart alterations
- Authors
- Moysés-Oliveira, M., Giannuzzi, G., Fish, R.J., Rosenfeld, J.A., Petit, F., de Fatima Soares, M., Kulikowski, L.D., Battista, A.D., 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.
- ID
- ZDB-PUB-171204-36
- Date
- 2017
- Source
- Human Mutation 39(2): 281-291 (Journal)
- Registered Authors
- Fish, Richard, Neerman-Arbez, Marguerite
- Keywords
- AMMECR1, X-linked disease, bone dysplasia, growth delay, heart alteration
- MeSH Terms
-
- 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
- PubMed
- 29193635 Full text @ Hum. Mutat.
Citation
Moysés-Oliveira, M., Giannuzzi, G., Fish, R.J., Rosenfeld, J.A., Petit, F., de Fatima Soares, M., Kulikowski, L.D., Battista, A.D., 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. (2017) Inactivation of AMMECR1 is associated with growth, bone and heart alterations. Human Mutation. 39(2):281-291.
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 co-expressed 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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping