ArticleAnnals of neurology2014
Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome.
Article in Annals of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Endosomal system genetics and autism spectrum disorders: A literature review.Neuroscience and biobehavioral reviews · 2016Pooled it
- Integrative structural analysis of human endosomal NHE6 reveals a lipid-associated gate and disordered C-terminus.Nature communications · 2026Article
- Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.Nature communications · 2026Article
- The Recycling Endosomal (NaActa physiologica (Oxford, England) · 2026Article
- Endosome maturation is orchestrated by inside-out proton signaling through a NaNature communications · 2026Article
- Endosome maturation is orchestrated by inside-out proton signaling through a NaResearch square · 2026Article
- Christianson Syndrome Family Experiences: Results From Caregiver Interviews.Journal of child neurology · 2025Article
- Retrospective Reports of Skill Attainment and Loss in Phelan-McDermid Syndrome.American journal on intellectual and developmental disabilities · 2025Article
- Missense variants in SLC9A6 cause partial epilepsy without neurodevelopmental delay.Orphanet journal of rare diseases · 2025Article
- Alterations in the NaCerebellum (London, England) · 2025Article
- Article
- Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults.Journal of medical genetics · 2024Article
- Atlantoaxial Instability due to Os Odontoideum in a Child with Christianson Syndrome.Molecular syndromology · 2024Article
- GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.The Journal of biological chemistry · 2024Article
- Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity.American journal of human genetics · 2024Article
- Functional analysis of two SLC9A6 frameshift variants in lymphoblastoid cells from patients with Christianson syndrome.CNS neuroscience & therapeutics · 2023Article
- Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in a haploid in vitro cell model.Biology open · 2023Article
- Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability.BMC neurology · 2023Article
- Slc9a6 mutation causes Purkinje cell loss and ataxia in the shaker rat.Human molecular genetics · 2023Article
- Pain research and children and adolescents with severe intellectual disability: ethical challenges and imperatives.The Lancet. Child & adolescent health · 2023Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveRecently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). We aimed to determine the diagnostic criteria and mutational spectrum for CS.
methodsTwelve independent pedigrees (14 boys, age = 4-19 years) with mutations in NHE6 were administered standardized research assessments, and mutations were characterized.
resultsThe mutational spectrum was composed of 9 single nucleotide variants, 2 indels, and 1 copy number variation deletion. All mutations were protein-truncating or splicing mutations. We identified 2 recurrent mutations (c.1498 c>t, p.R500X; and c.1710 g>a, p.W570X). Otherwise, all mutations were unique. In our study, 7 of 12 mutations (58%) were de novo, 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.
interpretationThis 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.
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