Adrenoleukodystrophy: Incidence, new mutation rate, and results of extended family screening
Adrenoleukodystrophy: Incidence, new mutation rate, and results of extended family screening
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DOI：
10.1002/ana.101
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发表时间：
2001-04-01
影响因子：
11.2
通讯作者：
Moser, HW
中科院分区：
文献类型：
--
作者：
Bezman, L;Moser, AB;Moser, HW
利用血浆极长链脂肪酸测定，辅以突变分析和免疫荧光测定，我们确定了在美国进行大部分测定的两个实验室每年鉴定的X-连锁肾上腺脑白质营养不良（X-ALD）半合子的数量：肯尼迪克里格研究所1981年至1998年和马约诊所罗切斯特1996年至1998年。在美国鉴定的半合子的最低频率估计为1：42，000，半合子加杂合子的最低频率估计为1：16，800。我们的研究涉及616个家系，共有12，787名确定的高危成员。在4，169名高危人群（33%）中进行了诊断检测，其中包括大家庭成员。只有5%的男性先证者和1.7%的X-ALD半合子被发现有新的突变。大家族检测鉴定出594个半合子和1,270个杂合子。新发现的半合子中有250例无症状，代表了治疗成功机会最大的一组。杂合子的鉴定为通过遗传咨询进行疾病预防提供了机会。诊断测试应提供给所有有风险的亲属的X-ALD患者，并应包括大家庭的成员。
Utilizing the plasma very long chain fatty acid assay, supplemented by mutation analysis and immunofluorescence assay, we determined the number of X-linked adrenoleukodystrophy (X-ALD) hemizygotes from the United States identified each year in the two laboratories that perform most of the assays in this country: the Kennedy Krieger Institute between 1981 and 1998 and the Mayo Clinic Rochester from 1996 to 1998. The minimum frequency of hemizygotes identified in the United States is estimated to be 1:42,000 and that of hemizygotes plus heterozygotes 1:16,800. Our studies involved 616 pedigrees with a total of 12,787 identified at-risk members. Diagnostic assays were performed in 4,169 at-risk persons (33%) and included members of the extended family. Only 5% of male probands and 1.7% of X-ALD hemizygotes were found to have new mutations. The extended family testing led to the identification of 594 hemizygotes and 1,270 heterozygotes. Two hundred fifty of the newly identified hemizygotes were asymptomatic and represent the group in which therapy has the greatest chance of success. Identification of heterozygotes provides the opportunity for disease prevention through genetic counseling. Diagnostic tests should be offered to all at-risk relatives of X-ALD patients and should include members of the extended family.