What is Nalcn gene mutation?

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.

What is Clifahdd?

Definition. CLIFAHDD is a congenital disorder characterized by congenital contractures of the limbs and face, resulting in characteristic facial features, hypotonia, and variable degrees of developmental delay.

Where are the mutations in the NALCN gene?

The first 6 mutations were found by exome sequencing, and subsequent mutations were found by sequencing the NALCN gene in 202 samples from patients with a similar disorder. All of the mutations were located in or near the predicted S5 and S6 segments of the protein, which are part of the pore-forming domain.

Is the NALCN gene responsible for facial dystonia?

This study found a plausible association, though not statistically confirmed, of cervical dystonia with SNPs in the NALCN region. NALCN is the gene responsible for INAD with facial dysmorphism Two mutations, one missense and one nonsense, in NALCN in two unrelated families.

Which is a pathogenic variant of the NALCN channel?

Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties. Intellectual disability-associated UNC80 mutations reveal inter-subunit interaction and dendritic function of the NALCN channel complex.

What is the role of NALCN in sodium leak?

NALCN forms a voltage-independent, nonselective, noninactivating cation channel permeable to Na+, K+, and Ca (2+). It is responsible for the neuronal background sodium leak conductance ( Lu et al., 2007 ). Lee et al. (1999) cloned rat Nalcn, which encodes a protein with the 4-domain structure of voltage-gated Ca (2+) and Na+ channels.