Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 4, 1003-1010, 13 March 2008
doi:10.1016/j.ajhg.2008.01.013
Report
SLC9A6 Mutations Cause X-Linked Mental Retardation, Microcephaly, Epilepsy, and Ataxia, a Phenotype Mimicking Angelman Syndrome
Gregor D. Gilfillan1, 2, 15, Kaja K. Selmer1, 2, 15, Ingrid Roxrud3, Raffaella Smith4, Mårten Kyllerman5, Kristin Eiklid1, Mette Kroken1, Morten Mattingsdal1, Thore Egeland1, Harald Stenmark3, Hans Sjøholm6, Andres Server7, Lena Samuelsson8, Arnold Christianson9, Patrick Tarpey4, Annabel Whibley10, Michael R. Stratton4, P. Andrew Futreal4, Jon Teague4, Sarah Edkins4, Jozef Gecz11, Gillian Turner12, F. Lucy Raymond10, Charles Schwartz13, Roger E. Stevenson13, Dag E. Undlien1, 2 and Petter Strømme2, 14, 
, 
1 Department of Medical Genetics, Ullevål University Hospital, NO-0407 Oslo, Norway
2 Faculty Division, Ullevål University Hospital, Faculty of Medicine, University of Oslo, NO-0316 Oslo, Norway
3 Department of Biochemistry, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, NO-0310 Oslo, Norway
4 Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK
5 The Queen Silvia Children's Hospital, Gothenburg University, S-416 85 Gothenburg, Sweden
6 Section for Neurophysiology, Department of Neurology, Ullevål University Hospital, NO-0407 Oslo, Norway
7 Department of Neuroradiology, Ullevål University Hospital, NO-0407 Oslo, Norway
8 Department of Clinical Genetics, Sahlgrenska University Hospital, Gothenburg University, S-416 85 Gothenburg, Sweden
9 Division of Human Genetics, National Health Laboratory Service and University of Witwatersrand, Johannesburg 2000, South Africa
10 Cambridge Institute of Medical Research, Cambridge, CB2 0XY, UK
11 Neurogenetics Laboratory, Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, SA 5006, Australia
12 Hunter Genetics and University of Newcastle, Newcastle, NSW 2300, Australia
13 Greenwood Genetic Center, JC Self Research Institute of Human Genetics, Greenwood, SC 29646, USA
14 Department of Pediatrics, Ullevål University Hospital, NO-0407 Oslo, Norway
Corresponding author15 These authors contributed equally to this work.
Abstract
Linkage analysis and DNA sequencing in a family exhibiting an X-linked mental retardation (XLMR) syndrome, characterized by microcephaly, epilepsy, ataxia, and absent speech and resembling Angelman syndrome, identified a deletion in the SLC9A6 gene encoding the Na+/H+ exchanger NHE6. Subsequently, other mutations were found in a male with mental retardation (MR) who had been investigated for Angelman syndrome and in two XLMR families with epilepsy and ataxia, including the family designated as having Christianson syndrome. Therefore, mutations in SLC9A6 cause X-linked mental retardation. Additionally, males with findings suggestive of unexplained Angelman syndrome should be considered as potential candidates for SLC9A6 mutations.
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