A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21
A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21
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DOI：
10.1136/jmg.2005.031880
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发表时间：
2006-05-01
影响因子：
4
通讯作者：
Crow, YJ
中科院分区：
文献类型：
--
作者：
Ali, M;Highet, LJ;Crow, YJ
背景资料：Aicardi-Goutieres综合征（AGS）是一种常染色体隐性遗传的早发性脑病，其特征为基底节钙化、慢性脑脊液淋巴细胞增多和常见产前感染的血清学检查阴性。AGS可能是干扰素α代谢紊乱的结果。该疾病是遗传异质性与约50%的家庭映射到第一个已知的位点在3 p21（AGS 1）。方法：全基因组扫描进行了10个家庭的临床诊断AGS在其中连锁AGS 1已被排除。在感兴趣的区域进行了更高密度的基因分型，使用10个映射家系和7个额外的AGS family.Results：我们的研究结果表明显着的连锁第二AGS基因座（AGS 2）在染色体13 q14 -21与最大的多点异质性对数的赔率（LOD）得分为5.75在D13 S768。AGS 2位点位于4.7 cM区域内定义的1 LOD单位的支持interval.Conclusions：我们已经确定了第二个AGS疾病位点和至少一个进一步的位点。在许多其他条件下，遗传异质性是AGS基因鉴定的一个重大障碍。AGS 2的本地化是这一进程中的重要一步。
Background: Aicardi-Goutieres syndrome (AGS) is an autosomal recessive, early onset encephalopathy characterised by calcification of the basal ganglia, chronic cerebrospinal fluid lymphocytosis, and negative serological investigations for common prenatal infections. AGS may result from a perturbation of interferon a metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1).Methods: A genome-wide scan was performed in 10 families with a clinical diagnosis of AGS in whom linkage to AGS1 had been excluded. Higher density genotyping in regions of interest was also undertaken using the 10 mapping pedigrees and seven additional AGS families.Results: Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14-21 with a maximum multipoint heterogeneity logarithm of the odds (LOD) score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region as defined by a 1 LOD-unit support interval.Conclusions: We have identified a second AGS disease locus and at least one further locus. As in a number of other conditions, genetic heterogeneity represents a significant obstacle to gene identification in AGS. The localisation of AGS2 represents an important step in this process.