RESUMO
Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.
Assuntos
Encefalopatias/genética , Calcinose/genética , Predisposição Genética para Doença , Mutação , Doenças Neurodegenerativas/genética , Adulto , Idoso , Alelos , Transporte Biológico , Biomarcadores , Encefalopatias/diagnóstico , Encefalopatias/metabolismo , Calcinose/diagnóstico , Calcinose/metabolismo , Linhagem Celular Tumoral , China , Feminino , Genes sis , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/metabolismo , Neuroimagem , Fenótipo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptores Acoplados a Proteínas G/genética , Receptores Virais/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Tomografia Computadorizada por Raios X , Receptor do Retrovírus Politrópico e XenotrópicoRESUMO
OBJECTIVE: To investigate the prevalence of unintended pregnancy (UP) and exploring the risk factors of UP for married women of child-bearing age from Qingshan district, Wuhan. METHODS: A cross-sectional study was adopted in this study. Cluster sampling method was used with 3256 women recruited, in 2010. Information on history and risks related to social-demographic factors of UP were collected, using a self-administered questionnaire. RESULTS: Of the 3256 participants, over half of them (53.8%) reorted ever having had the history of UP and 9.1% reported UP in the past year. Rate of UP in the past year for different age cohorts (18-30, 31-40, 41-49 years) were 31.8%, 10.5% and 1.8% respectively. The most frequently reported reason for UP across all the age cohorts was "Did not use any contraceptive methods", with proportions on the reason that reported by women at 18-30, 31-40 and 41-49 year-olds, were 69.7%, 51.1% and 42.4% respectively. The second frequently reported reasons for UP were "Failure of traditional contraception" for younger cohort (18-30 years: 13.0%) and "IUD dropped or pregnancy with IUD" for older-age cohorts (23.4% at 31-40 year-olds and 37.0% at the 41-49 year-olds). The most frequently cited reason for "Did not use any contraceptive methods" was "Believe we were lucky so far, not to get pregnant" (59.6%). The risk factors of UP were being at older age, experiencing sex debut at younger age and got married at younger age. CONCLUSION: The prevalence of lifetime UP history was high among women at child-bearing age from Qingshan district, Wuhan. Reproductive health services and interventions should be taken according to the needs from different age cohorts of women. Younger cohort of women should receive more attention.