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Publication Details

Title :

Phenotypic and Molecular Spectrum of Aicardi-Goutières Syndrome: A Study of 24 Patients.

Journal:

Pediatr Neurol.

Impact Factor:

1.866

Authors:

Al Mutairi F1, Alfadhel M2, Nashabat M2, El-Hattab AW3, Ben-Omran T4, Hertecant J3, Eyaid W2, Ali R4, Alasmari A5, Kara M6, Al-Twaijri W7, Filimban R5, Alshenqiti A8, Al-Owain M8, Faqeih E5, Alkuraya FS9.

Affiliations:

1 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. Electronic address: dr.fmutairi@gmail.com.

2 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.

3 Division of Clinical Genetics and Metabolic Disorders, Tawam Hospital, Al Ain, United Arab Emirates.

4 Division of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Qatar.

5 Medical Genetics Section, King Fahad Medical City, Children’s Hospital, Riyadh, Saudi Arabia.

6 Department of Pediatrics, University of Tripoli, Tripoli, Libya.

7 King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Division of Neurology, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.

8 Department of Medical Genetics, King Faisal Specialist Hospital, and Research Center, Riyadh, Saudi Arabia.

9 Department of Medical Genetics, King Faisal Specialist Hospital, and Research Center, Riyadh, Saudi Arabia; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

Year of Publication:

2018

DOI:

10.1016/j.pediatrneurol.2017.09.002.

Abstract:

BACKGROUND:
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.

MATERIALS AND METHODS:
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.

RESULTS:
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.

CONCLUSIONS:
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.