Submission Details

Autosomal recessive

09/10/2019

The PREPL gene is located on chromosome 2 at 2p21 and encodes the prolyl endopeptidase like protein, which encodes a putative serine peptidase from the prolyl oligopeptidase family. The protein is ubiquitously expressed with higher levels found in the brain, kidney, and muscle, however, the biological role of the PREPL is yet to be fully elucidated. PREPL was first reported in relation to autosomal recessive isolated PREPL-related myasthenic syndrome, congenital in 2018 (28726805: Regal et al. 2018). Evidence supporting this gene-disease relationship includes case-level data and experimental data. At least six unique variants including deletion, frameshift, and splice variants have been reported in four probands from three publications (28726805: Regal et al. 2018; 29483676: Silva et al. 2018; 29913539: Laugwitz et al. 2018). All variants were found in either a homozygous state or a compound heterozygous state with a second deleterious variant. This gene-disease relationship is supported by expression studies that demonstrate colocalization of PREPL with alpha bungarotoxin within muscle fibers and at the endplates (24610330: Regal et al. 2014) and Prepl knockout mice that recapitulate the key features of the disorder including stunted growth and neonatel hypotonia which resolves over time (24586561: Lone et al. 2014). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.

28726805 29483676 29913539 24610330 24586561