title: Deletion of the parkin and PACRG gene promoter in early-onset parkinsonism.
abstract: Autosomal recessive mutations in the parkin gene (PARK2) have been identified as a common cause of familial and also sporadic, early-onset parkinsonism (EOPD): point mutations, exonic deletions, and duplications or triplications have been described. Here we report a novel mutation, consisting of a deletion of the promoter and exon 1 of parkin (c.1-?_7+?del), in a family compatible with autosomal recessive EOPD and an isolated case. The former was compound heterozygous for the parkin c.1-?_7+?del mutation and an exon 3 deletion (c.172-?_412+?del). The latter was homozygous for the parkin c.1-?_7+?del mutation. The promoter region is shared by parkin and the neighboring parkin coregulated gene (PACRG), which are oriented head-to-head and are transcribed on opposite DNA strands. There were no parkin transcripts in lymphoblasts from the patients carrying the parkin c.1-?_7+?del mutation. The phenotypes of patients with promoter deletions and consequently absence of parkin and possibly PACRG expression, were similar to and no more severe than those of other EOPD patients with parkin mutations.
authors.affiliation: INSERM U679, Neurology and Experimental Therapeutics, Centre Hospitalier Universitaire (CHU) Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lesage
authors.forename: Periquet
authors.initials: P
authors.lastname: Magali
authors.forename: Ebba
authors.initials: E
authors.lastname: Lohmann
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: Helio
authors.initials: H
authors.lastname: Teive
authors.forename: Sabine
authors.initials: S
authors.lastname: Janin
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Cousin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D011401:Promoter Regions, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D008840:Microfilament Proteins; D018832:Molecular Chaperones; C471711:PACRG protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein