Homozygous deletions in parkin gene in European and North African families with autosomal recessive juvenile parkinsonism
Homozygous deletions in parkin gene in European and North African families with autosomal recessive juvenile parkinsonism
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DOI：
10.1016/s0140-6736(05)60746-5
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发表时间：
1998-10-24
期刊：
影响因子：
168.9
通讯作者：
Brice, A
中科院分区：
文献类型：
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作者：
Lücking, CB;Abbas, N;Brice, A
1998年1月至5月，在疟疾传播不稳定的肯尼亚东北部的非免疫人群中发生了恶性疟疾的大流行。由于厄尔尼诺现象，1996年和1997年旱灾期间恶性疟原虫低度传播，1997年11月至12月发生大降雨和洪灾，自1952年以来，该地区从未报告过这样的暴发。1998年3月底，我们对瓦吉尔的疫情进行了回顾调查，瓦吉尔是一个有60000居民的城镇。审查了瓦吉尔政府医院和卫生部以及无国界医生流动诊所的监测数据。我们使用两阶段整群抽样调查对1月1日至3月8日期间的死亡率进行了回顾性评估。为了评估疑似疟疾病例的临床和寄生虫学状况，在流动诊所进行了横断面调查，系统抽样了五分之一的患者。病例被定义为居住在Wajir镇的任何患者，在排除其他原因后，最近有发烧病史。与外显子8-9缺失的患者相比，有发病的趋势(39[11]比13[6]年，p<；0·01)，并且在相似的病程中有更严重的趋势(Hoehn和Yahr评分：3·6[1·1]比2·6[0·9])。这两个缺失都可能导致移码，引入过早的终止密码子，并应该导致截断的蛋白质，可能会失去功能。外显子3的缺失可能有更多的有害影响，导致更短的截断蛋白，因为这些患者受到的影响更严重。然而，外显子8-9的缺失与发病年龄较早有关，似乎较少截断的蛋白质会导致额外的毒性效应。在具有不同类型突变的患者中，进一步的表型和基因型相关性将有助于澄清这个问题。
From January to May, 1998, a major epidemic of Plasmodium falciparum malaria occurred in a non-immune population in north-eastern Kenya, an area of unstable malaria transmission. This epidemic happened after low transmission of P falciparum during 1996 and 1997 droughts, followed by major rainfall and floods in November to December, 1997, due to El Niño. Such an outbreak had not been reported since 1952 in this area. At the end of March, 1998, we investigated retrospectively the outbreak in Wajir, a town of 60000 inhabitants. Surveillance data from Wajir Government Hospital and Ministry of Health and Médecins Sans Frontières mobile clinics were reviewed. We used a twostage cluster-sampling survey to assess mortality retrospectively during Jan 1 to March 8. To assess the clinical and parasitological status of suspected malaria cases, a cross-sectional survey was carried out at mobile clinics, with systematic sampling of a fifth of patients. A case was defined as any patient living in Wajir town with a recent history of fever, after exclusion of other causes. A onset than those with exon 8–9 deletions (39 [11] vs 13 [6] years, p< 0· 01), and a trend towards greater severity for similar disease durations (Hoehn and Yahr score: 3· 6 [1· 1] vs 2· 6 [0· 9]). Both deletions are expected to cause frameshifts introducing a premature stop codon and should result in truncated proteins with probable loss of function. The exon 3 deletion might have more harmful effects, leading to a shorter truncated protein, since these patients are more severely affected. The exon 8–9 deletion is, however, associated with earlier age at onset, as if the less truncated protein results in an additional toxic effect. Further phenotype and genotype correlations in patients with different types of mutations will help to clarify this question.