ArticlePLoS genetics2009
CA8 mutations cause a novel syndrome characterized by ataxia and mild mental retardation with predisposition to quadrupedal gait.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Expanding the spectrum of ATP8A2 mutations: a new splicing variant and systematic review of CAMRQ4 syndrome.Molecular biology reports · 2025Pooled it
- Insights from cerebellar transcriptomic analysis into the pathogenesis of ataxia.JAMA neurology · 2014Trial
- Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred.Genome research · 2011Trial
- Carbonic anhydrase VIII as a regulator of intracellular calcium signaling: mechanistic insights and implications in human disease.Molecular biology reports · 2026Review
- Purkinje cell intrinsic activity shapes cerebellar development and function.Nature communications · 2026Article
- Applications of Carbonic Anhydrase Inhibitors in Neurological Disorders, Mechanisms and Therapeutic Potential.Sub-cellular biochemistry · 2026Review
- Mitochondrial DNA copy number reduction viaEpigenomics · 2026Article
- Identification of a Novel VLDLR Variant in the First Report of CAMRQ1 From Africa: Expanding the Spectrum of Cerebellar Ataxia Syndromes.Human mutation · 2026Article
- Unveiling Carbonic Anhydrase VIII, X, XI Expression in Cancer and Neurological Diseases Through Integrated Bioinformatics Approaches.Bioinformatics and biology insights · 2026Article
- Cerebellar deep brain stimulation rescues Purkinje cell mitochondrial density in a genetic mouse model of cerebellar ataxia.Brain research bulletin · 2026Article
- Making sense of carbonic anhydrase function in zebrafish using antisense morpholinos.Molecular genetics and genomics : MGG · 2025Review
- Biosafety and efficacy of Kv7 activating rdHSV-CA8∗ analgesic gene therapy for chronic pain via the intra-articular route in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function.Nature communications · 2025Article
- TMEM106B deficiency leads to alterations in lipid metabolism and obesity in the TDP-43Communications biology · 2025Article
- Regulation of transcription patterns, poly(ADP-ribose), and RNA-DNA hybrids by the ATM protein kinase.Cell reports · 2024Article
- A-T neurodegeneration and DNA damage-induced transcriptional stress.DNA repair · 2024Review
- rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- Disease-modifying rdHSV-CA8* non-opioid analgesic gene therapy treats chronic osteoarthritis pain by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- Regulation of transcription patterns, poly-ADP-ribose, and RNA-DNA hybrids by the ATM protein kinase.bioRxiv : the preprint server for biology · 2023Article
- Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We describe a consanguineous Iraqi family in which affected siblings had mild mental retardation and congenital ataxia characterized by quadrupedal gait. Genome-wide linkage analysis identified a 5.8 Mb interval on chromosome 8q with shared homozygosity among the affected persons. Sequencing of genes contained in the interval revealed a homozygous mutation, S100P, in carbonic anhydrase related protein 8 (CA8), which is highly expressed in cerebellar Purkinje cells and influences inositol triphosphate (ITP) binding to its receptor ITPR1 on the endoplasmatic reticulum and thereby modulates calcium signaling. We demonstrate that the mutation S100P is associated with proteasome-mediated degradation, and thus presumably represents a null mutation comparable to the Ca8 mutation underlying the previously described waddles mouse, which exhibits ataxia and appendicular dystonia. CA8 thus represents the third locus that has been associated with quadrupedal gait in humans, in addition to the VLDLR locus and a locus at chromosome 17p. Our findings underline the importance of ITP-mediated signaling in cerebellar function and provide suggestive evidence that congenital ataxia paired with cerebral dysfunction may, together with unknown contextual factors during development, predispose to quadrupedal gait in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.