Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NALCN and its homologues code for the ion channel responsible for half of background Na(+) -leak conductance in vertebrate and invertebrate neurons. Recessive mutations in human NALCN cause intellectual disability (ID) with hypotonia. Here, we report a de novo heterozygous mutation in NALCN affecting a conserved residue (p.R1181Q) in a girl with ID, episodic and persistent ataxia, and arthrogryposis. Interestingly, her episodes of ataxia were abolished by the administration of acetazolamide, similar to the response observed in episodic ataxia associated with other ion channels. Introducing the analogous mutation in the Caenorhabditis elegans homologue nca-1 induced a coiling locomotion phenotype, identical to that obtained with previously characterized C. elegans gain-of-function nca alleles, suggesting that p.R1181Q confers the same property to NALCN. This observation thus suggests that dominant mutations in NALCN can cause a neurodevelopmental phenotype that overlaps with, while being mostly distinct from that associated with recessive mutations in the same gene.
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PMID:A Gain-of-Function Mutation in NALCN in a Child with Intellectual Disability, Ataxia, and Arthrogryposis. 2586 27

Mutation in NALCN (Sodium leak channel, non-selective) gene in humans has been shown to present with a wide spectrum of clinical manifestations including neurodevelopmental impairment, hypotonia and congenital contractures. Distinctive features including episodic ataxia and neuroaxonal dystrophy have also been reported. In this case report, we describe the muscle biopsy findings of a 3-year-old boy who presented with congenital arthrogryposis, hypotonia and developmental delay who has a heterozygous de novo C.965T>C (p.1332T) variant in the NALCN gene found by expanded whole exome sequencing (WES). Distal arthrogryposis and ulnar deviation of hands were prominent findings, which have been shown to be associated with de novo heterozygous mutations in this gene. He also presented with brief paroxysmal episodes of tremulousness; however, he has not clearly had episodes of episodic ataxia. Initial work-up including extensive genetic and metabolic tests was normal except for mildly elevated multiple metabolites in urine, suggestive of mild dysfunction of multiple mitochondrial enzymes. Muscle biopsy findings revealed ragged red fiber changes on trichrome staining and an increased number of mitochondria with non-specific crystalloid like inclusions ultrastructurally. The biochemical and muscle biopsy findings are suggestive of a possible mitochondrial bioenergetic dysfunction. The association of NALCN gene with secondary mitochondrial dysfunction remains unclear.
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PMID:Muscle biopsy findings in a child with NALCN gene mutation. 2747 21