The Results of Whole Exome Sequencing Performed On Previously Undiagnosed Pediatric Neurology Patients
Iranian Journal of Child Neurology,
Vol. 15 No. 2 (2021),
8 March 2021
Whole exome sequencing (WES) is a new molecular diagnostic test, used in pediatric medicine, especially pediatric neurology. The diagnostic yield of WES is higher than conventional methods. Therefore, this study aimed to assess the diagnostic yield of WES in a pediatric neurology clinic and to report positive results.
Materials & Methods
This retrospective study was performed on patients, presenting to the pediatric neurology clinic of Ghaem Hospital in Mashhad, Iran, between March 2015 and March 2017, with various neurological disabilities and unrevealing workup before WES. The patients’ clinical features and molecular diagnoses based on the WES
were reported in this study. The overall diagnostic yield of WES was 82.71% (67/81 patients). Two patients were excluded for the lack of data. Sixty-five patients with pathogenic or possibly pathogenic variants exhibited various abnormalities, including intellectual disability/developmental delay (n=44), seizure (n=27), developmental regression (n=11), myopathy (n=9), microcephaly (n=8), neuropathy (n=2), autism spectrum
disorder (n=2), and neuromuscular disease (n=2). Overall, 93.84% of the patients were born to consanguineous parents. Also, 62 patients had an autosomal recessive disorder, and three patients had an autosomal
The present findings indicating the high diagnostic yield of WES, besides the important role of this test in determining the etiology of non-specific and atypical presentations of genetic disorders, support the use of WES in pediatric neurology practice.
- whole exome sequencing
- diagnostic yield
- pediatric neurology
How to Cite
Gropman AL, Batshaw ML. Epigenetics, copy number variation, and other molecular mechanisms underlying neurodevelopmental disabilities: new insights and diagnostic approaches. Journal of Developmental & Behavioral Pediatrics. 2010;31(7):582-91.
Fogel BL, Satya-Murti S, Cohen BH. Clinical exome sequencing in neurologic disease. Neurology: Clinical Practice. 2016;6(2):164-76.
Shashi V, McConkie-Rosell A, Rosell B, Schoch K, Vellore K, McDonald M, et al. The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders. Genetics in Medicine. 2013;16(2):176-82.
Livingston J. Next generation child neurologists. Developmental Medicine & Child Neurology. 2015;57(1):4-5.
Kuperberg M, Lev D, Blumkin L, Zerem A, Ginsberg M, Linder I, et al. Utility of whole exome sequencing for genetic diagnosis of previously undiagnosed pediatric neurology patients. Journal of child neurology. 2016;31(14):1534-9.
Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, et al. Clinical whole exome sequencing in child neurology practice. Annals of neurology. 2014;76(4):473-83.
Dixon-Salazar TJ, Silhavy JL, Udpa N, et al. Exome sequencing can improve diagnosis and alter patient management. Sci Transl Med. 2012;4(138):138ra78.
Liberski PP, Blackstone C. Hereditary Spastic Paraplegia. Neurodegeneration. 2017:161.
Rehman AU, Najafi M, Kambouris M, Al‐Gazali L, Makrythanasis P, Rad A, et al. Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function. Human mutation. 2018.
Castro-Gago M, Dacruz-Alvarez D, Pintos-Martínez E, Beiras-Iglesias A, Arenas J, Martín MÁ, et al. Congenital neurogenic muscular atrophy in megaconial myopathy due to a mutation in CHKB gene. Brain and Development. 2016;38(1):167-72.
Stessman HA, Xiong B, Coe BP, Wang T, Hoekzema K, Fenckova M, et al. Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nature genetics. 2017;49(4):515.
Monies D, Abouelhoda M, AlSayed M, Alhassnan Z, Alotaibi M, Kayyali H, et al. The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. Human genetics. 2017;136(8):921-39.
Atwal PS, Brennan M-L, Cox R, Niaki M, Platt J, Homeyer M, et al. Clinical whole-exome sequencing: are we there yet? Genetics in Medicine. 2014;16(9):717-9.
Yang Y, Muzny DM, Reid JG, et al. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N Engl J Med 2013; 369:1502–1511.
Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic acids research. 2017;46(D1):D1062-D7.
Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, et al. Protein-truncating mutations in ASPM cause variable reduction in brain size. The American Journal of Human Genetics. 2003;73(5):1170-7.
Muhammad F, Mahmood Baig S, Hansen L, Sajid Hussain M, Anjum Inayat I, Aslam M, et al. Compound heterozygous ASPM mutations in Pakistani MCPH families. American journal of medical genetics Part A. 2009;149(5):926-30.
Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461(7261):272-6.
De Ligt J, Willemsen MH, Van Bon BW, Kleefstra T, Yntema HG, Kroes T, et al. Diagnostic exome sequencing in persons with severe intellectual disability. New England Journal of Medicine. 2012;367(20):1921-9.
Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, et al. Exome sequencing identifies the cause of a mendelian disorder. Nature genetics. 2010;42(1):30-5.
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