Homozygous Missense Variation in Causes Prenatal-Onset Severe Neurodegeneration.

The patatin-like protein family plays an important role in various biological functions including lipid homeostasis, cellular growth, and signaling. Conserved across species, the patatin domain is shared by all 9 members of the PNPLA family without redundancy in the coding sequences. The defective function of , , and are known to cause mitochondrial-related neurodegeneration. Recently, has been associated with mitochondrial myopathy and poor weight gain with lactic acidosis in 3 unrelated families. Using whole-exome sequencing, we identified a homozygous novel missense variation c.1874A>G in the patatin domain of . The patient had prenatal-onset severe and progressive neurodegeneration with mortality in infancy.