Submission Details

Autosomal recessive

12/10/2019

The PMPCB gene is located on chromosome 7 at 7q22.1 and encodes the mitochondrial processing beta peptidase, which is the catalytic subunit of mitochondrial processing protease (MPP) and is required for proteolytic processing of mitochondrial proteins. The PMPCB gene was first reported in relation to autosomal recessive PMPCB-related multiple mitochondrial dysfunctions syndrome in 2018 (29576218: Vögtle et al. 2018). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Five missense variants in this gene have been reported in a compound heterozygous or homozygous state in four unrelated probands in one publication (29576218: Vögtle et al. 2018). The clinical phenotype was characterized by neurodegeneration in childhood with cerebellar atrophy. The proposed disease mechanism is that biallelic variants in PMPCB cause defects in MPP proteolytic activity and leads to dysregulation of iron-sulfur (Fe-S) cluster biogenesis. The gene-disease relationship is supported by biochemical function data and functional alteration in yeast and patient cells (25970558: Quiros et al. 2015; 29576218: Vögtle et al. 2018). 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.

25970558 29576218