Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Denmark.
Acta Paediatr. 2012 Nov;101(11):e509-13. doi: 10.1111/j.1651-2227.2012.02807.x. Epub 2012 Sep 5.
The aim of the study was to identify the genetic background for Aicardi-Goutieres syndrome (AGS) in the Faroe Islands.
Four patients with AGS were identified. The patients had a variable phenotype, from a severe prenatal form with intrauterine foetal death to a milder phenotype, albeit still with an early onset, within the first 2-3 months.
A genome-wide search for homozygosity revealed one single 15.6 Mb region of homozygosity on chromosome 13, which included RNASEH2B, where a splice site mutation c.322-3C>G was identified. Screening of 170 anonymous Faroese controls revealed a carrier frequency of approximately 1.8%, corresponding to an incidence of AGS in the Faroe Islands of around 1 in 12,300.
The previously identified RNASEH2B mutations comprise altogether 20 mutations (missense, nonsense and splice site) with all patients harbouring at least one missense mutation. The severe phenotype of the Faroese patients compared with the previously reported patients with RNASEH2B mutations may be caused by the presence of two null alleles (although some residual normal splicing cannot be ruled out), whereas patients with one or two missense mutations may have some, albeit abnormal, RNASEH2B proteins, and hence some residual activity of RNASEH2B, explaining their milder phenotype.
本研究旨在确定法罗群岛 Aicardi-Goutières 综合征（AGS）的遗传背景。
鉴定了 4 名 AGS 患者。这些患者具有不同的表型，从严重的产前宫内胎儿死亡到更轻微的表型，尽管仍有早发型，发生在第 2-3 个月内。
全基因组搜索发现 13 号染色体上有一个 15.6Mb 的纯合子区域，其中包括 RNASEH2B，存在剪接位点突变 c.322-3C>G。对 170 名匿名法罗群岛对照者进行筛查发现，携带者频率约为 1.8%，这相当于法罗群岛 AGS 的发病率约为每 12300 人中 1 例。
先前鉴定的 RNASEH2B 突变共包括 20 个突变（错义、无义和剪接位点），所有患者均携带至少一个错义突变。法罗群岛患者的严重表型与先前报道的 RNASEH2B 突变患者相比，可能是由于存在两个无义等位基因（尽管不能排除一些残留的正常剪接），而携带一个或两个错义突变的患者可能具有一些异常的 RNASEH2B 蛋白，因此具有一些残留的 RNASEH2B 活性，解释了他们较轻的表型。
