RGD Reference Report - Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay. - Rat Genome Database

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Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay.

Authors: Al-Sayed, Moeenaldeen D  Al-Zaidan, Hamad  Albakheet, Albandary  Hakami, Hana  Kenana, Rosan  Al-Yafee, Yusra  Al-Dosary, Mazhor  Qari, Alya  Al-Sheddi, Tarfa  Al-Muheiza, Muhammed  Al-Qubbaj, Wafa  Lakmache, Yamina  Al-Hindi, Hindi  Ghaziuddin, Muhammad  Colak, Dilek  Kaya, Namik 
Citation: Al-Sayed MD, etal., Am J Hum Genet. 2013 Oct 3;93(4):721-6. doi: 10.1016/j.ajhg.2013.08.001. Epub 2013 Sep 26.
RGD ID: 12914762
Pubmed: (View Article at PubMed) PMID:24075186
DOI: Full-text: DOI:10.1016/j.ajhg.2013.08.001

Sodium leak channel, nonselective (NALCN) is a voltage-independent and cation-nonselective channel that is mainly responsible for the leaky sodium transport across neuronal membranes and controls neuronal excitability. Although NALCN variants have been conflictingly reported to be in linkage disequilibrium with schizophrenia and bipolar disorder, to our knowledge, no mutations have been reported to date for any inherited disorders. Using linkage, SNP-based homozygosity mapping, targeted sequencing, and confirmatory exome sequencing, we identified two mutations, one missense and one nonsense, in NALCN in two unrelated families. The mutations cause an autosomal-recessive syndrome characterized by subtle facial dysmorphism, variable degrees of hypotonia, speech impairment, chronic constipation, and intellectual disability. Furthermore, one of the families pursued preimplantation genetic diagnosis on the basis of the results from this study, and the mother recently delivered healthy twins, a boy and a girl, with no symptoms of hypotonia, which was present in all the affected children at birth. Hence, the two families we describe here represent instances of loss of function in human NALCN.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Nalcn  (sodium leak channel, non-selective)

Genes (Mus musculus)
Nalcn  (sodium leak channel, non-selective)

Genes (Homo sapiens)
NALCN  (sodium leak channel, non-selective)


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