CLPP is a mitochondrial protease. Studies indicate that disturbances of mitochondrial protein homeostasis are the cause of CLPP-related disorders.
Perrault syndrome – CLPP-associated Perrault syndrome is caused by homozygous hypomorphic missense or splice variants. Compound heterozygous variants are presumed to be causative but none have been reported to date. CLPP pathogenic missense variants mostly localise to a region of CLPP from amino acid residue 142 to 162, with a cluster around residues 144-147.
Other CLPP-associated disorders – Severe neurological disorders associated with CLPP are caused by homozygous loss of function variants or compound heterozygous loss of function and missense variants. Loss of function variants in this case include frameshift variants and multi-exon deletions. Diagnostic testing – Due to the phenotypic overlap with other conditions, panel or exome testing is recommended.