Ali M, Highet L J, Lacombe D, Goizet C, King M D, Tacke U, van der Knaap M S, Lagae L, Rittey C, Brunner H G, van Bokhoven H, Hamel B, Oade Y A, Sanchis A, Desguerre I, Cau D, Mathieu N, Moutard M L, Lebon P, Kumar D, Jackson A P, Crow Y J
Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds, UK.
J Med Genet. 2006 May;43(5):444-50. doi: 10.1136/jmg.2005.031880. Epub 2005 May 20.
Aicardi-Goutières 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 alpha metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1).
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.
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.
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.
艾卡迪-古铁雷斯综合征（AGS）是一种常染色体隐性早发性脑病，其特征为基底神经节钙化、慢性脑脊液淋巴细胞增多，以及常见产前感染的血清学检查呈阴性。AGS可能是由α干扰素代谢紊乱引起的。该疾病具有遗传异质性，约50%的家系定位于3p21的第一个已知位点（AGS1）。
对10个临床诊断为AGS且已排除与AGS1连锁的家系进行全基因组扫描。还使用这10个定位家系和另外7个AGS家系对感兴趣区域进行了更高密度的基因分型。
我们的结果显示与位于13q14 - 21染色体的第二个AGS位点（AGS2）存在显著连锁，在D13S768处的最大多点异质性对数优势（LOD）评分为5.75。AGS2位点位于由1个LOD单位支持区间定义的4.7 cM区域内。
我们鉴定出了第二个AGS疾病位点以及至少一个其他位点。与许多其他疾病一样，遗传异质性是AGS基因鉴定的一个重大障碍。AGS2的定位是这一过程中的重要一步。
