Striking intrafamilial phenotypic variability in Aicardi–Goutières syndrome associated with the recurrent Asian founder mutation in RNASEH2C
Striking intrafamilial phenotypic variability in Aicardi–Goutières syndrome associated with the recurrent Asian founder mutation in RNASEH2C
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Aicardi-Goutières 综合征显着的家族内表型变异与 RNASEH2C 复发性亚洲创始人突变相关
DOI：
10.1002/ajmg.a.35712
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发表时间：
2013
影响因子：
2
通讯作者：
C. Oley
中科院分区：
文献类型：
--
作者：
J. Vogt;S. Agrawal;Zala Ibrahim;T. Southwood;S. Philip;L. Macpherson;Malini V. Bhole;Y. Crow;C. Oley
Aicardi-Goutières综合征（AGS）是一种常染色体隐性遗传的儿童早期脑病。该疾病表现出显着的遗传异质性，迄今已确定的五个基因中存在致病突变。尽管大多数AGS患者经历严重的新生儿或婴儿表现、不良的神经发育结果和降低的存活率，但越来越多地认识到该病症的发作和严重程度的临床变异性。特别是在与SAMHD 1和RNASEH 2B突变相关的情况下，观察到对发育、发病率和死亡率具有更可变影响的后期表现。相比之下，复发性c.205C > T（p.R69W）RNASEH 2C亚洲创始者突变先前仅在具有严重AGS表型的儿童中鉴定。在这里，据我们所知，我们提出了显着的表型变异的兄弟姐妹都窝藏在纯合子状态下的创始人突变的第一份报告。在这个家庭中，一个女孩有一个严重的AGS表型，在婴儿期发病，严重的发育迟缓，而一个姐姐是完全正常的智力与正常的头围，只是诊断，因为存在冻疮和轻度偏瘫。家庭内的表型表达的赞赏是重要的咨询家庭考虑产前诊断，也可能是相关的疗效评估，在未来的临床试验。此外，显著的表型变异增加了目前未发现更多轻度受影响患者的可能性。© 2013威利期刊公司.
Aicardi–Goutières syndrome (AGS) is an encephalopathy of early childhood which is most commonly inherited as an autosomal recessive trait. The disorder demonstrates significant genetic heterogeneity with causative mutations in five genes identified to date. Although most patients with AGS experience a severe neonatal or infantile presentation, poor neurodevelopmental outcome and reduced survival, clinical variability in the onset and severity of the condition is being increasingly recognized. A later presentation with a more variable effect on development, morbidity and mortality has been particularly observed in association with mutations in SAMHD1 and RNASEH2B. In contrast, the recurrent c.205C > T (p.R69W) RNASEH2C Asian founder mutation has previously only been identified in children with a severe AGS phenotype. Here, to our knowledge, we present the first report of marked phenotypic variability in siblings both harboring this founder mutation in the homozygous state. In this family, one female child had a severe AGS phenotype with an onset in infancy and profound developmental delay, whilst an older sister was of completely normal intellect with a normal head circumference and was only diagnosed because of the presence of chilblains and a mild hemiplegia. An appreciation of intrafamilial phenotypic expression is important in the counseling of families considering prenatal diagnosis, and may also be relevant to the assessment of efficacy in future clinical trials. In addition, marked phenotypic variation raises the possibility that more mildly affected patients are not currently identified. © 2013 Wiley Periodicals, Inc.
影响因子：
9.8
作者：
Rice, Gillian;Newman, William G.;Crow, Yanick J.
通讯作者：
Crow, Yanick J.
影响因子：
9.8
作者：
Rice, Gillian;Patrick, Teresa;Crow, Yanick J.
通讯作者：
Crow, Yanick J.
影响因子：
14.9
作者：
Jeong, HS;Backlund, PS;Crouch, RJ
通讯作者：
Crouch, RJ