Referenced in: none

Automatically associated channels: Kir6.2

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

Authors: Moeenaldeen D Al-Sayed, Hamad Al-Zaidan, AlBandary AlBakheet, Hana Hakami, Rosan Kenana, Yusra Al-Yafee, Mazhor Al-Dosary, Alya Qari, Tarfa Al-Sheddi, Muhammed Al-Muheiza, Wafa Al-Qubbaj, Yamina Lakmache, Hindi Al-Hindi, Muhammad Ghaziuddin, Dilek Colak, Namik Kaya

Journal, date & volume: Am. J. Hum. Genet., 2013 Oct 3 , 93, 721-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24075186

Abstract
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.