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Inactivation of AMMECR1 is associated with growth, bone, and heart alterations. Hum Mutat 2018 02;39(2):281-291 PMID: 29193635

Pubmed ID

29193635

DOI

10.1002/humu.23373

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.

Author List

Moysés-Oliveira M, Giannuzzi G, Fish RJ, Rosenfeld JA, Petit F, Soares MF, Kulikowski LD, Di-Battista A, Zamariolli M, Xia F, Liehr T, Kosyakova N, Carvalheira G, Parker M, Seaby EG, Ennis S, Gilbert RD, Hagelstrom RT, Cremona ML, Li WL, Malhotra A, Chandrasekhar A, Perry DL, Taft RJ, McCarrier J, Basel DG, Andrieux J, Stumpp T, Antunes F, Pereira GJ, Neerman-Arbez M, Meloni VA, Drummond-Borg M, Melaragno MI, Reymond A

Author

Donald Basel MD Chief, Associate Professor in the Pediatrics department at Medical College of Wisconsin




Scopus

2-s2.0-85038010872   3 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Bone and Bones
Cell Cycle
Cell Line
Exome
Female
HeLa Cells
Heart
Humans
Male
Proteins
Whole Genome Sequencing
Zebrafish
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70