biostudies-literatureEldomery MKCPRIT training ProgramThe Baden-Württemberg Stiftung and Emmy-Noether-Program (DFG)Deutsche Forschungsgemeinschaft (DFG)Prx1 antiserumFoundation for the National Institutes of HealthNHGRI NIH HHSNational Human Genome Research Institute (US)NIGMS NIH HHS106https://www.ebi.ac.uk/biostudies/studies/S-EPMC5088683biostudies-literatureUnknown8(1)<h4>Background</h4>Mitochondrial presequence proteases perform fundamental functions as they process about 70 % of all mitochondrial preproteins that are encoded in the nucleus and imported posttranslationally. The mitochondrial intermediate presequence protease MIP/Oct1, which carries out precursor processing, has not yet been established to have a role in human disease.<h4>Methods</h4>Whole exome sequencing was performed on four unrelated probands with left ventricular non-compaction (LVNC), developmental delay (DD), seizures, and severe hypotonia. Proposed pathogenic variants were confirmed by Sanger sequencing or array comparative genomic hybridization. Functional analysis of the identified MIP variants was performed using the model organism Saccharomyces cerevisiae as the protein and Genome medicineMIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death.PMC5088683T32 GM07526RP140102U54 HG006542T32 GM007526U54HG006542Rodenburg RJCharng WLRosenfeld JAJhangiani SNGibbs RABurrage LCBoerwinkle ETang JLalani SRRamachandran PVPenney SWang XLupski JRVogtle FNXia FGu SMuzny DMMulica PMedikonda RWong LJHertecant JMeisinger CAl Shamsi AGambin TEldomery MKAbdul-Rahman OAZimmerman HHWang MCYang YSutton VREng CMAkdemir ZCfalseMIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death.<h4>Background</h4>Mitochondrial presequence proteases perform fundamental functions as they process about 70 % of all mitochondrial preproteins that are encoded in the nucleus and imported posttranslationally. The mitochondrial intermediate presequence protease MIP/Oct1, which carries out precursor processing, has not yet been established to have a role in human disease.<h4>Methods</h4>Whole exome sequencing was performed on four unrelated probands with left ventricular non-compaction (LVNC), developmental delay (DD), seizures, and severe hypotonia. Proposed pathogenic variants were confirmed by Sanger sequencing or array comparative genomic hybridization. Functional analysis of the identified MIP variants was performed using the model organism Saccharomyces cerevisiae as the protein and 2016-01-01T00:00:00Z2016 Nov2025-04-04T20:24:08.632Z2019-03-27T02:27:56ZS-EPMC50886832779906410.1186/s13073-016-0360-6