{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:49:05Z","timestamp":1789040945860,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,19]],"date-time":"2014-09-19T00:00:00Z","timestamp":1411084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1-P20-GM103645-01A1"],"award-info":[{"award-number":["1-P20-GM103645-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Burroughs Wellcome Career Award for Medical Science"},{"name":"Chrisitanson Syndrome Association"},{"name":"Nancy Lurie Marks Foundation for Autism Research"},{"name":"Simons Foundation for Autism Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X\u2010linked Na\n                      <jats:sup>+<\/jats:sup>\n                      \/H\n                      <jats:sup>+<\/jats:sup>\n                      exchanger 6 (\n                      <jats:italic>NHE6<\/jats:italic>\n                      ). We aimed to determine the diagnostic criteria and mutational spectrum for CS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Twelve independent pedigrees (14 boys, age\u2009=\u20094\u201319 years) with mutations in\n                      <jats:italic>NHE6<\/jats:italic>\n                      were administered standardized research assessments, and mutations were characterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mutational spectrum was composed of 9 single nucleotide variants, 2 indels, and 1 copy number variation deletion. All mutations were protein\u2010truncating or splicing mutations. We identified 2 recurrent mutations (c.1498 c&gt;t, p.R500X; and c.1710 g&gt;a, p.W570X). Otherwise, all mutations were unique. In our study, 7 of 12 mutations (58%) were\n                      <jats:italic>de novo<\/jats:italic>\n                      , in contrast to prior literature wherein mutations were largely inherited. We also report prominent neurological, medical, and behavioral symptoms. All CS participants were nonverbal and had intellectual disability, epilepsy, and ataxia. Many had prior diagnoses of autism and\/or Angelman syndrome. Other neurologic symptoms included eye movement abnormalities (79%), postnatal microcephaly (92%), and magnetic resonance imaging evidence of cerebellar atrophy (33%). Regression was noted in 50%, with recurrent presentations involving loss of words and\/or the ability to walk. Medical symptoms, particularly gastrointestinal symptoms, were common. Height and body mass index measures were below normal ranges in most participants. Behavioral symptoms included hyperkinetic behavior (100%), and a majority exhibited high pain threshold.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This is the largest cohort of independent CS pedigrees reported. We propose diagnostic criteria for CS. CS represents a novel neurogenetic disorder with general relevance to autism, intellectual disability, Angelman syndrome, epilepsy, and regression. Ann Neurol 2014;76:581\u2013593<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24225","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T12:57:59Z","timestamp":1405429079000},"page":"581-593","source":"Crossref","is-referenced-by-count":82,"title":["Genetic and phenotypic diversity of\n                    <scp>\n                      <i>NHE<\/i>\n                    <\/scp>\n                    <i>6<\/i>\n                    mutations in\n                    <scp>C<\/scp>\n                    hristianson syndrome"],"prefix":"10.1002","volume":"76","author":[{"given":"Matthew F.","family":"Pescosolido","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Cell Biology, and Biochemistry and Laboratory for Molecular Medicine Institute for Brain Science, Brown University Providence RI"},{"name":"Developmental Disorders Genetics Research Program, Emma Pendleton Bradley Hospital and Department of Psychiatry and Human 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MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sabbagh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Cell Biology, and Biochemistry and Laboratory for Molecular Medicine Institute for Brain Science, Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Rogg","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging Warren Alpert Medical School of Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umadevi","family":"Tantravahi","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pathology, Woman and Infants Hospital Warren Alpert Medical School of Brown University Providence RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"McLean","sequence":"additional","affiliation":[{"name":"Developmental Disorders Genetics 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