NALCN channelopathies: Distinguishing gain-of-function and loss-of-function mutations.

ABSTRACT:

Objective

To perform genotype-phenotype analysis in an infant with congenital arthrogryposis due to a de novo missense mutation in the NALCN ion channel and explore the mechanism of pathogenicity using a Caenorhabditis elegans model.

Methods

We performed whole-exome sequencing in a preterm neonate with congenital arthrogryposis and a severe life-threatening clinical course. We examined the mechanism of pathogenicity of the associated NALCN mutation by engineering the orthologous mutation into the nematode C elegans using CRISPR-Cas9.

Results

We identified a de novo missense mutation in NALCN, c.1768C>T, in an infant with a severe neonatal lethal form of the recently characterized CLIFAHDD syndrome (congenital contractures of the limbs and face with hypotonia and devel

SUBMITTER: Bend EG 

PROVIDER: S-EPMC5027803 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature