THE UTILITY OF WHOLE EXOME SEQUENCING IN DIAGNOSING PEDIATRIC NEUROLOGICAL DISORDERS
Muthaffar OY
*Corresponding Author: Osama Y. Muthaffar, M.D., Department of Pediatrics, King Abdulaziz University, Jeddah, PO Box 80215, Jeddah 21589, Kingdom of Saudi Arabia. Tel.: +96-12-640-1000 (ext. 20208). Fax: 996-12-640-3975. E-mail: oymuthaffar@kau.edu.sa; osamam@hotmail.com
page: 17

RESULTS

There were 19 males and seven females included in the study. Age of presentation ranged from 1 to 12 years (mean 4.8 years). Nineteen patients had positive WES results (73.0%), five patients with variants of unknown significance (VUS) that matches the clinical picture, one patient with VUS that does not explain the observed clinical characteristics. The remaining six patients were negative. The average age in the WES-positive group was 4.9 years and the average age in the WES-negative group was 4.5 years. Consanguinity was positive in 69.0% of the cohort, most of them were in the WES-positive group (Table 2). The WES-positive cohort results were classified into pathogenic, likely pathogenic variants and VUS. In the homozygous and heterozygous groups, pathogenic and likely pathogenic mutations were found. These mutations, when paired with the phenotype, confirms the clinical picture (Tables 3 and 4). The VUS group was mainly clinically upgraded to clinically significant variants as those patients have matched genotype and phenotype. No benign or likely benign variants were detected in this cohort. Eight patients had homozygous mutations, six patients had heterozygous mutations and six patients were carrying VUS. All patients had variable neurological presentations such as: epilepsy, intellectual delay, motor delay, regression of milestones, hypotonia, visual abnormalities, ataxia and MRI brain changes. Similar family history in another sibling or relative was reported in seven patients with positive WES result. One patient had ITGA7 classified as VUS that does not explain the phenotype. He was developmentally normal then developed regression of milestones and a middle cerebral artery stroke after meningoencephalitis. An ITGA7 mutation was reported to be associated with congenital muscular dystrophy, neonatal hypotonia, proximal atrophy and scoliosis ,which were not apparent in this patient before his regression. Variants of unknown significance with consistent phenotypes were seen in five patients (Table 3). The MLC1 mutation in patient #16 was consistent with megalencephalic leukoencephalopathy with subcortical cysts type 1. The patient developed ataxia and convulsions. Brain MRI also showed expected white matter changes and temporal cysts. Patient #17 had a SLC6A3 mutation compatible with infantile Parkinsonism-dystonia type 1. He presented with orolingual, upper and lower limbs dystonia and was initially diagnosed as cerebral palsy. Patient #18 was diagnosed with intractable infantile spasms and failed to respond to multiple antiseizure medications for several months. He also developed regression of milestones. A PNPO mutation was reported once. He was put on pyridoxal 5 phosphate cofactor therapy. No more seizures were reported by the parents and he is now developmentally up to age after 1 year of follow-up. Targeted analysis of both parents showed heterozygous mutations in both (Figure 1). Patient #19 was found to have ataxia and oculomotor apraxia. Brain MRI showed classic molar tooth sign. The CC2D2A mutation is associated with Joubert syndrome. Patient #20 had infantile onset of developmental delay, hearing impairment, hypotonia, visual impairment, focal epilepsy, high serum lactic acid and brain MRI showed brain atrophy. Mutations in SPATA5 and TIMMDC1 were reported to cause epilepsy, hearing loss, and mental retardation syndrome and mitochondrial complex I deficiency, respectively.



Number 26
Number 26 VOL. 26(2), 2023 All in one
Number 26
VOL. 26(2), 2023
Number 26
VOL. 26, 2023 Supplement
Number 26
VOL. 26(1), 2023
Number 25
VOL. 25(2), 2022
Number 25
VOL. 25 (1), 2022
Number 24
VOL. 24(2), 2021
Number 24
VOL. 24(1), 2021
Number 23
VOL. 23(2), 2020
Number 22
VOL. 22(2), 2019
Number 22
VOL. 22(1), 2019
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006