Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease

• DOI: 10.1073/pnas.1419581111
• Publication Date: 2014-11-25T04:48:51Z
• Authors: Hilal Unal Gulsuner; Suleyman Gulsuner; Fatma Nazli Mercan; Onur Emre Onat; Tom Walsh; Hashem Shahin; Ming K. Lee; Okan Dogu; Tulay Kansu; Haluk Topaloglu; Bulent Elibol; Cenk Akbostanci; Mary-Claire King; Tayfun Ozcelik; Ayse B. Tekinay
• Keywords: Male; genomic DNA; sequence analysis; 150; Neurodegenerative disease; mouse mutant; 0302 clinical medicine; middle aged; population dynamics; mitochondrion; DNA sequencing; Child; motoneuron; Aged, 80 and over; child; clinical article; HtrA2 gene; adult; Serine Endopeptidases; allele; Parkinson Disease; High-Temperature Requirement A Serine Peptidase 2; Middle Aged; enzyme activity; Mitochondria; Pedigree; 3. Good health; homozygote; Parkinson disease; Mitochondrial Dysfunction; Science & Technology - Other Topics; Female; onset age; Adult; Dna Sequencing; serine proteinase Omi; Adolescent; Essential Tremor; animal experiment; gene frequency; Article; Mitochondrial Proteins; pedigree analysis; Young Adult; 03 medical and health sciences; Humans; controlled study; Gene Identification; human; essential tremor; gene; mouse; Aged; nonhuman; Neurodegenerative Disease; animal model; missense mutation; heterozygote; relative; Gene identification; Mutation; homozygosity; Mitochondrial dysfunction; exome

Significance Essential tremor is one of the most frequent movement disorders humans, but its causes remain largely unknown. In a six-generation family with both essential and Parkinson disease, we identified rare missense mutation HTRA2 as causative allele. Family members homozygous for this allele were more severely affected than those heterozygous The same had been associated characteristics in mouse mutants disease some, not all, epidemiologic studies. Our results suggest that may be responsible some families homozygosity damaging alleles disease.