GEOGRAPHICAL-DISTRIBUTION OF TTR MET(30) CARRIERS IN NORTHERN SWEDEN - DISCREPANCY BETWEEN CARRIER FREQUENCY AND PREVALENCE RATE
GEOGRAPHICAL-DISTRIBUTION OF TTR MET(30) CARRIERS IN NORTHERN SWEDEN - DISCREPANCY BETWEEN CARRIER FREQUENCY AND PREVALENCE RATE
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DOI：
10.1136/jmg.31.5.351
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发表时间：
1994-05-01
影响因子：
4
通讯作者：
COSTA, PP
中科院分区：
文献类型：
--
作者：
HOLMGREN, G;COSTA, PMP;COSTA, PP
瑞典首例家族性淀粉样变性多发性神经病(FAP)于1965年发表。在瑞典的FAP患者中也发现了与日本、葡萄牙和其他人群中相同的转甲状腺激素(TTRMet(30))突变。瑞典北部已诊断出350多名有FAP临床症状的患者，其中大多数来自Skellefta和Pitea周围地区。患者的平均发病年龄为56岁，远远晚于来自日本和葡萄牙的患者。为了估计Vasterbotten县和Norrbotten县TTRMet(30)突变的频率，从健康计划(Monica)中随机抽取1276名年龄在24岁至65岁之间的人的血清，用单抗FD6进行筛查。在19人中，13名女性和6名男性在使用该抗体的酶联免疫吸附试验中呈阳性反应。DNA分析证实TTRMet(30)突变，18例为杂合子，1例为纯合子。在这项研究中没有寻找其他突变。该地区23个亚群的TTRMet(30)携带者平均频率为1.5%，范围为0.0~8.3%。TTRMET(30)等位基因的地区分布与FAP的发病率有显著差异。在该地区50万总人口中，TTRMET(30)基因携带者的估计数量约为7500人。TTRMet(30)突变的外显率在不同家系之间表现出相当大的差异，在该人群中的总体诊断(预测)价值低至约2%。
The first Swedish case of familial amyloidotic polyneuropathy (FAP) was published in 1965. The same transthyretin (TTR met(30)) mutation as that seen in Japanese, Portuguese, and other populations was also found in Swedish FAP patients. More than 350 patients with clinical manifestations of FAP have been diagnosed in northern Sweden, most of them originating from the areas around Skelleftea and Pitea. The mean age of onset is 56 years, much later than in patients from Japan and Portugal. To estimate the frequency of the TTR met(30) mutation in the counties of Vasterbotten and Norrbotten, sera from 1276 persons aged 24 to 65 years, randomly sampled from a health programme (MONICA), were screened with the monoclonal antibody FD6. In 19 persons, 13 females and six males, a positive reaction was seen in an Elisa test using this antibody. DNA analysis confirmed the TTR met(30) mutation and showed that 18 were heterozygous and one homozygous for this mutation. Other mutations were not looked for in this study. The mean TTR met(30) Carrier frequency in the area was 1.5% ranging from 0.0 to 8.3% in 23 subpopulations. There was a notable discrepancy between the regional distribution of the TTR met(30) allele and the morbidity rate for FAP. The estimated number of TTR met(30) gene carriers in a total population of 500 000 in the area is approximately 7500. The penetrance of the TTR met(30) mutation shows considerable variation between families, and the overall diagnostic (predictive) value in this population is as low as around 2%.