RESUMO
Mutations in the Grb10-interacting GYF protein 2 (GIGYF2) gene, within the PARK11 locus, have been nominated as a cause of Parkinson's disease in Italian and French populations. By sequencing the whole GIGYF2 coding region in forty-six probands (thirty-seven Italians) with familial Parkinson's disease compatible with an autosomal dominant inheritance, we identified no mutations. Our data add to a growing body of evidence suggesting that GIGYF2 mutations are not a frequent cause of PD.
Assuntos
Proteínas de Transporte/genética , Doença de Parkinson/genética , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Mutação , LinhagemRESUMO
BACKGROUND AND OBJECTIVES: This study explored variations in the clinical manifestations of intravascular lymphoma (IVL) on the bases of the association with hemophagocytosis and the country where the diagnosis was made. DESIGN AND METHODS: The clinical features of 50 Western patients with IVL were compared with those of 123 patients with IVL diagnosed in Eastern countries (87 diagnosed in Japan and 36 in other Asian countries), previously reported in English literature, and collected by an electronic bibliographic search. RESULTS: Hemophagocytosis was absent in Western patients, but reported in 38 (44%) Japanese patients (p=0.00001) and in seven (19%) patients from other Asian countries (p=0.002). No clinical differences were evident between patients with hemophagocytosis-negative IVL diagnosed in Western countries, Japan and other Asian Countries. Conversely, Japanese and non-Japanese patients with hemophagocytosis-related IVL more frequently had stage IV disease, fever, hepato-splenic involvement, marrow infiltration, dyspnea, anemia, and thrombocytopenia, and rarely exhibited cutaneous or central nervous system involvement. Lymph node and peripheral blood involvement was uncommon in all subgroups. In Western patients, anthracycline-based chemotherapy was associated with a 52% remission rate, and a 2-year overall survival of 46%. INTERPRETATION AND CONCLUSIONS: The clinical features of IVL vary according to the association with hemophagocytosis, regardless of the country in which the diagnosis is made. Western, Japanese and other Asian patients with hemophagocytosis-negative IVL display similar clinical characteristics and should be considered as having classical IVL. Patients with hemophagocytosis-related IVL show significantly different clinical features. Both forms have a poor prognosis. Extensive molecular studies are needed to explore whether these clinical differences might reflect discordant biological entities within IVL.
Assuntos
Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Neoplasias Vasculares/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ásia/epidemiologia , Povo Asiático/estatística & dados numéricos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Previsões , Humanos , Japão/etnologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etnologia , Linfo-Histiocitose Hemofagocítica/etiologia , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/etnologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Fenótipo , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Inquéritos e Questionários , Resultado do Tratamento , Neoplasias Vasculares/classificação , Neoplasias Vasculares/complicações , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/etnologia , Neoplasias Vasculares/patologia , População Branca/estatística & dados numéricosRESUMO
A multiethnic series of patients with early-onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype-genotype relationships. Forty-six EOP probands with an onset age of < 45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost-effective, real-time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11-3C > G, and exon 8-9-10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work-up of EOP.
