Selenoprotein biosynthesis defect causes progressive encephalopathy with elevated lactate.

ABSTRACT:

Objective

We aimed to decipher the molecular genetic basis of disease in a cohort of children with a uniform clinical presentation of neonatal irritability, spastic or dystonic quadriplegia, virtually absent psychomotor development, axonal neuropathy, and elevated blood/CSF lactate.

Methods

We performed whole-exome sequencing of blood DNA from the index patients. Detected compound heterozygous mutations were confirmed by Sanger sequencing. Structural predictions and a bacterial activity assay were performed to evaluate the functional consequences of the mutations. Mass spectrometry, Western blotting, and protein oxidation detection were used to analyze the effects of selenoprotein deficiency.

Results

Neuropathology indicated laminar necrosis and severe loss of myelin,

SUBMITTER: Anttonen AK 

PROVIDER: S-EPMC4520820 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature