BACKGROUND AND PURPOSE: To evaluate the phenotype and the frequencies of mutations in PRKN, DJ1 and PINK1 genes in patients with Parkinson disease (PD) in Turkey. METHODS: Eighty-six patients from 77 PD families participated in the study. Seventy-four families were originating from Turkey, two families from Greece and one family from Bulgaria. All patients underwent detailed neurological examination. PRKN, PINK1 and DJ1 genes were sequenced, and dosage analysis was performed by multiplex ligation-dependent probe amplification. RESULTS: Sixteen patients with PD were found to carry homozygous (n = 14) or compound heterozygous (n = 2) PRKN mutations. We identified exon rearrangements, three point mutations and one new point mutation in exon 2 (p.K27del). In two families, two new PINK1 point mutations (L31X and P416L) were identified. No pathogenic mutations were found in DJ1 gene. Clinical phenotypes of PRKN patients were comparable to previously described features, but only in four of 13 families, the pedigree structure was clearly consistent with an autosomal recessive (AR) mode of inheritance in comparison with nine families where also different pattern of transmission could have been possible. CONCLUSIONS: Our data suggest that the PRKN gene mutation is the most frequent form of ARPD in Turkey. The proportion of mutations with regard to the age of onset in our population is in the range of those previously described, but our pedigrees are characterized by high rate of consanguinity, which might explain the high proportion of families with homozygous mutations and of patients in more than one generation. Pathogenic DJ1 mutations do not seem to play a major role in Turkey.
BACKGROUND AND PURPOSE: To evaluate the phenotype and the frequencies of mutations in PRKN, DJ1 and PINK1 genes in patients with Parkinson disease (PD) in Turkey. METHODS: Eighty-six patients from 77 PD families participated in the study. Seventy-four families were originating from Turkey, two families from Greece and one family from Bulgaria. All patients underwent detailed neurological examination. PRKN, PINK1 and DJ1 genes were sequenced, and dosage analysis was performed by multiplex ligation-dependent probe amplification. RESULTS: Sixteen patients with PD were found to carry homozygous (n = 14) or compound heterozygous (n = 2) PRKN mutations. We identified exon rearrangements, three point mutations and one new point mutation in exon 2 (p.K27del). In two families, two new PINK1 point mutations (L31X and P416L) were identified. No pathogenic mutations were found in DJ1 gene. Clinical phenotypes of PRKNpatients were comparable to previously described features, but only in four of 13 families, the pedigree structure was clearly consistent with an autosomal recessive (AR) mode of inheritance in comparison with nine families where also different pattern of transmission could have been possible. CONCLUSIONS: Our data suggest that the PRKN gene mutation is the most frequent form of ARPD in Turkey. The proportion of mutations with regard to the age of onset in our population is in the range of those previously described, but our pedigrees are characterized by high rate of consanguinity, which might explain the high proportion of families with homozygous mutations and of patients in more than one generation. Pathogenic DJ1 mutations do not seem to play a major role in Turkey.
Authors: Suzanne Lesage; Ariane Lunati; Marion Houot; Sawssan Ben Romdhan; Fabienne Clot; Christelle Tesson; Graziella Mangone; Benjamin Le Toullec; Thomas Courtin; Kathy Larcher; Mustapha Benmahdjoub; Mohammed Arezki; Ahmed Bouhouche; Mathieu Anheim; Emmanuel Roze; François Viallet; François Tison; Emmanuel Broussolle; Murat Emre; Hasmet Hanagasi; Basar Bilgic; Meriem Tazir; Mouna Ben Djebara; Riadh Gouider; Christine Tranchant; Marie Vidailhet; Eric Le Guern; Olga Corti; Chokri Mhiri; Ebba Lohmann; Andrew Singleton; Jean-Christophe Corvol; Alexis Brice Journal: Ann Neurol Date: 2020-05-30 Impact factor: 10.422
Authors: Manuela M X Tan; Naveed Malek; Michael A Lawton; Leon Hubbard; Alan M Pittman; Theresita Joseph; Jason Hehir; Diane M A Swallow; Katherine A Grosset; Sarah L Marrinan; Nin Bajaj; Roger A Barker; David J Burn; Catherine Bresner; Thomas Foltynie; John Hardy; Nicholas Wood; Yoav Ben-Shlomo; Donald G Grosset; Nigel M Williams; Huw R Morris Journal: Brain Date: 2019-09-01 Impact factor: 13.501
Authors: Vinicius M Fava; Yong Zhong Xu; Guillaume Lettre; Nguyen Van Thuc; Marianna Orlova; Vu Hong Thai; Shao Tao; Nathalie Croteau; Mohamed A Eldeeb; Emma J MacDougall; Geison Cambri; Ramanuj Lahiri; Linda Adams; Edward A Fon; Jean-François Trempe; Aurélie Cobat; Alexandre Alcaïs; Laurent Abel; Erwin Schurr Journal: Proc Natl Acad Sci U S A Date: 2019-07-15 Impact factor: 11.205
Authors: Suzanne Lesage; Ariane Lunati; Marion Houot; Sawssan Ben Romdhan; Fabienne Clot; Christelle Tesson; Graziella Mangone; Benjamin Le Toullec; Thomas Courtin; Kathy Larcher; Mustapha Benmahdjoub; Mohamed Arezki; Ahmed Bouhouche; Mathieu Anheim; Emmanuel Roze; François Viallet; François Tison; Emmanuel Broussolle; Murat Emre; Hasmet Hanagasi; Basar Bilgic; Meriem Tazir; Mouna Ben Djebara; Riadh Gouider; Christine Tranchant; Marie Vidailhet; Eric Le Guern; Olga Corti; Chokri Mhiri; Ebba Lohmann; Andrew Singleton; Jean-Christophe Corvol; Alexis Brice Journal: Ann Neurol Date: 2020-07-28 Impact factor: 11.274