King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.
King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.
Pediatr Neurol. 2018 Jan;78:35-40. doi: 10.1016/j.pediatrneurol.2017.09.002. Epub 2017 Oct 5.
Aicardi-Goutières syndrome is a rare genetic neurological disorder with variable clinical manifestations. Molecular detection of specific mutations is required to confirm the diagnosis. The aim of this study was to review the clinical and molecular diagnostic findings in 24 individuals with Aicardi-Goutières syndrome who presented during childhood in an Arab population.
We reviewed the records of 24 patients from six tertiary hospitals in different Arab countries. All included patients had a molecular diagnosis of Aicardi-Goutières syndrome.
Six individuals with Aicardi-Goutières syndrome (25%) had a neonatal presentation, whereas the remaining patients presented during the first year of life. Patients presented with developmental delay (24 cases, 100%); spasticity (24 cases, 100%); speech delay (23 cases, 95.8%); profound intellectual disability (21 cases, 87.5%); truncal hypotonia (21 cases, 87.5%); seizures (eighteen cases, 75%); and epileptic encephalopathy (15 cases, 62.5%). Neuroimaging showed white matter abnormalities (22 cases, 91.7%), cerebral atrophy (75%), and small, multifocal calcifications in the lentiform nuclei and deep cerebral white matter (54.2%). Homozygous mutations were identified in RNASEH2B (54.2%), RNASEH2A (20.8%), RNASEH2C (8.3%), SAMHD1 (8.3%), TREX1 (4.2%), and heterozygous mutations in IFIH1 (4.2%), with c.356A>G (p.Asp119Gly) in RNASEH2B being the most frequent mutation. Three novel mutations c.987delT and c.625 + 1G>A in SAMHD1 gene and c.961G>T in the IFIHI1 gene were identified.
This is the largest molecularly confirmed Aicardi-Goutières syndrome cohort from Arabia. By presenting these clinical and molecular findings, we hope to raise awareness of Aicardi-Goutières syndrome and to demonstrate the importance of specialist referral and molecular diagnosis.
Aicardi-Goutières 综合征是一种罕见的遗传性神经疾病，临床表现多样。需要检测特定突变的分子才能确诊。本研究旨在回顾在阿拉伯人群中，24 名儿童期起病的 Aicardi-Goutières 综合征患者的临床和分子诊断结果。
我们回顾了来自阿拉伯地区 6 家三级医院的 24 名患者的病历。所有纳入的患者均经分子诊断为 Aicardi-Goutières 综合征。
6 名 Aicardi-Goutières 综合征患者（25%）表现为新生儿起病，其余患者在 1 岁以内起病。患者表现为发育迟缓（24 例，100%）、痉挛（24 例，100%）、言语发育迟缓（23 例，95.8%）、重度智力障碍（21 例，87.5%）、躯干张力减退（21 例，87.5%）、癫痫发作（18 例，75%）和癫痫性脑病（15 例，62.5%）。神经影像学显示白质异常（22 例，91.7%）、脑萎缩（75%）和豆状核和深部脑白质多发小灶性钙化（54.2%）。RNASEH2B（54.2%）、RNASEH2A（20.8%）、RNASEH2C（8.3%）、SAMHD1（8.3%）、TREX1（4.2%）基因的纯合突变和 IFIH1（4.2%）基因的杂合突变均被检出，其中 RNASEH2B 基因的 c.356A>G（p.Asp119Gly）突变最为常见。发现了 3 个新突变 c.987delT、c.625+1G>A 和 c.961G>T，分别位于 SAMHD1 基因和 IFIHI1 基因。
这是来自阿拉伯地区的最大的经分子证实的 Aicardi-Goutières 综合征队列。通过呈现这些临床和分子发现，我们希望提高对 Aicardi-Goutières 综合征的认识，并展示专科转诊和分子诊断的重要性。
