Article (Scientific journals)
Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8.
Boycott, Kym M.; Beaulieu, Chandree L.; Kernohan, Kristin D. et al.
2015In American Journal of Human Genetics, 97 (6), p. 886-93
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Abstract :
[en] Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development.
Disciplines :
Pediatrics
Neurology
Genetics & genetic processes
Author, co-author :
Boycott, Kym M.
Beaulieu, Chandree L.
Kernohan, Kristin D.
Gebril, Ola H.
Mhanni, Aziz
Chudley, Albert E.
Redl, David
Qin, Wen
Hampson, Sarah
Kury, Sebastien
Tetreault, Martine
Puffenberger, Erik G.
Scott, James N.
Bezieau, Stephane
Reis, Andre
Uebe, Steffen
Schumacher, Johannes
Hegele, Robert A.
McLeod, D. Ross
Galvez-Peralta, Marina
Majewski, Jacek
RAMAEKERS, Vincent ;  Centre Hospitalier Universitaire de Liège - CHU > Centre de référence de l'autisme
Nebert, Daniel W.
Innes, A. Micheil
Parboosingh, Jillian S.
Abou Jamra, Rami
More authors (16 more) Less
Language :
English
Title :
Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8.
Publication date :
03 December 2015
Journal title :
American Journal of Human Genetics
ISSN :
0002-9297
eISSN :
1537-6605
Publisher :
University of Chicago Press, United States - Illinois
Volume :
97
Issue :
6
Pages :
886-93
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Available on ORBi :
since 22 February 2016

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