Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8

Boycott KM, Beaulieu CL, Kernohan KD, Gebril OH, Mhanni A, Chudley AE, Redl D, Qin W, Hampson S, Kuery S, Tetreault M, Puffenberger EG, Scott JN, Bezieau S, Reis A, Uebe S, Schumacher J, Hegele RA, Mcleod DR, Galvez-Peralta M, Majewski J, Ramaekers VT, Nebert DW, Innes AM, Parboosingh JS, Abou Jamra R (2015)

Publication Type: Journal article

Publication year: 2015

Journal

American Journal of Human Genetics Elsevier (Cell Press)

Publisher: Elsevier (Cell Press)

Book Volume: 97

Pages Range: 886-93

Journal Issue: 6

DOI: 10.1016/j.ajhg.2015.11.002

Abstract

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.

Authors with CRIS profile

André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Steffen Uebe Institute of Human Genetics

Involved external institutions

University of Ottawa CA Canada (CA) National Research Centre (NRC) / المركز القومي للبحوث EG Egypt (EG) University of Manitoba CA Canada (CA) University of Calgary CA Canada (CA) Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU) FR France (FR) McGill University CA Canada (CA) Clinic for Special Children US United States (USA) (US) Foothills Medical Centre (FMC) CA Canada (CA) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Robarts Research Institute CA Canada (CA) University of Cincinnati US United States (USA) (US)

How to cite

APA:

Boycott, K.M., Beaulieu, C.L., Kernohan, K.D., Gebril, O.H., Mhanni, A., Chudley, A.E.,... Abou Jamra, R. (2015). Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8. American Journal of Human Genetics, 97(6), 886-93. https://dx.doi.org/10.1016/j.ajhg.2015.11.002

MLA:

Boycott, Kym M., et al. "Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8." American Journal of Human Genetics 97.6 (2015): 886-93.

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