title: A Novel Homozygous p.L539F Mutation Identified in PINK1 Gene in a Moroccan Patient with Parkinsonism.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ten of fifteen causative genes linked to familial forms of PD have been reported to cause autosomal recessive forms. Among them, mutations in the PTEN-induced kinase 1 (PINK1) gene were shown to be responsible for a phenotype characterized by early onset, good response to levodopa, and a benign course. Using chromosomal microarray analysis and Sanger sequencing, we identified a homozygous G/C substitution in a 58-year-old Moroccan man diagnosed with recessive inherited Parkinson's disease. This G-to-C transition occurred at position 1617 leading to an amino acid change L/F at position 539 located in highly conserved motif in the C terminal sequence of PINK1. Interestingly, the c.1617G>C substitution is absent in 192 ethnically matched control chromosomes. Our findings have shown that the p.L539F is a novel mutation located in the C terminal sequence of the PINK1 protein that could be pathogenic and responsible for a clinical phenotype resembling idiopathic Parkinson's disease with rapid progression and early cognitive impairment.
authors.affiliation: Research Team on Neurodegenerative Diseases, Medical School and Pharmacy, Mohammed V University, 10100 Rabat, Morocco.
authors.forename: Rafiqua
authors.initials: R
authors.lastname: Ben El Haj
authors.affiliation: Research Team on Neurodegenerative Diseases, Medical School and Pharmacy, Mohammed V University, 10100 Rabat, Morocco; Department of Neurology and Neurogenetics, Specialties Hospital, CHU Ibn Sina, 10100 Rabat, Morocco.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Regragui
authors.affiliation: Laboratory of Biotechnology, Medical School and Pharmacy, Mohammed V University, 10100 Rabat, Morocco.
authors.forename: Rachid
authors.initials: R
authors.lastname: Tazi-Ahnini
authors.affiliation: Research Team on Neurodegenerative Diseases, Medical School and Pharmacy, Mohammed V University, 10100 Rabat, Morocco.
authors.forename: Asmae
authors.initials: A
authors.lastname: Skalli
authors.affiliation: Department of Neurology and Neurogenetics, Specialties Hospital, CHU Ibn Sina, 10100 Rabat, Morocco.
authors.forename: Naima
authors.initials: N
authors.lastname: Bouslam
authors.affiliation: Research Team on Neurodegenerative Diseases, Medical School and Pharmacy, Mohammed V University, 10100 Rabat, Morocco; Department of Neurology and Neurogenetics, Specialties Hospital, CHU Ibn Sina, 10100 Rabat, Morocco.
authors.forename: Ali
authors.initials: A
authors.lastname: Benomar
authors.affiliation: Research Team on Neurodegenerative Diseases, Medical School and Pharmacy, Mohammed V University, 10100 Rabat, Morocco; Department of Neurology and Neurogenetics, Specialties Hospital, CHU Ibn Sina, 10100 Rabat, Morocco.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Yahyaoui
authors.affiliation: Research Team on Neurodegenerative Diseases, Medical School and Pharmacy, Mohammed V University, 10100 Rabat, Morocco; Department of Neurology and Neurogenetics, Specialties Hospital, CHU Ibn Sina, 10100 Rabat, Morocco.
authors.forename: Ahmed
authors.identifier: 0000-0001-5279-8649
authors.initials: A
authors.lastname: Bouhouche
mesh_terms: D020816:Amino Acid Motifs; D002875:Chromosomes / Q000648:ultrastructure; D003072:Cognition Disorders / Q000235:genetics; D019295:Computational Biology; D018450:Disease Progression; D005091:Exons; D006720:Homozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009018:Morocco; D009154:Mutation; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000072417:Protein Domains; D011494:Protein Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007980:Levodopa; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase; C495280:LRRK2 protein, human