Exploring the Genetic Landscape of Diphtheria, Tetanus Toxoid, and Pertussis Vaccination Associated Seizures or Epilepsies
Abstract number :
V.097
Submission category :
12. Genetics / 12A. Human Studies
Year :
2021
Submission ID :
1826005
Source :
www.aesnet.org
Presentation date :
12/9/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:51 AM
Authors :
Sandeep Negi, PhD - Post Graduate Institute of Medical Education & Research, Chandigarh; JITENDRA SAHU – Post Graduate Institute of Medical Education & Research, Chandigarh; Prateek Bhatia – Post Graduate Institute of Medical Education & Research, Chandigarh; ANUPRIYA KAUR – Post Graduate Institute of Medical Education & Research, Chandigarh; Prahbhjot Malhi – Post Graduate Institute of Medical Education & Research, Chandigarh; Gagandeep Singh – Post Graduate Institute of Medical Education & Research, Chandigarh; Amit Arora – Post Graduate Institute of Medical Education & Research, Chandigarh; Navneen Sankhyan – Post Graduate Institute of Medical Education & Research, Chandigarh; Parampreet Kharbanda – Post Graduate Institute of Medical Education & Research, Chandigarh
Rationale: Diphtheria, Tetanus and Pertussis (DTP) vaccination associated seizures and subsequent epilepsy are the fundamental reason for the vaccine hesitancy and a barrier to the successful implementation of universal immunization. This study explores genetic explanation for susceptibility of a child for DTP vaccination seizure and subsequent epilepsy.
Methods: We enrolled 54 children with a history of first seizure within 72 hours of DTP vaccine from March 2017 to March 2019. We performed quantitative phenotyping and applied Vineland Social Maturity Scale-Indian Adaptation for neurodevelopment assessment. DNA extracted from blood was used for sequencing using a custom capture kit on Illumina sequencing platform with mean >80X coverage. Sequences obtained were aligned to GRCh37/hg19 using Burrows-Wheeler Aligner. Genome Analysis Toolkit was used to identify variants that were filtered using various databases like 1000Genome, and multiple algorithms such as PolyPhen-2 were used to find a variant effect. We reported variants using the American College of Medical Genetics guideline.
Results: We found pathogenic variants in 36 (67%) children, of which 17 (47%) were novel having 27 single-nucleotide polymorphism, 6 indels and 3 splice-site variants. All the 36 variants were having heterozygous inheritance and except the two being X-linked. The majority of pathogenic variants were found in SCN1A gene (n=21/36; 64%), SCN8A in 2 cases, and 13 other genes having one each variant in CDKL5, CPA6, DEPDC5, GNAO1, ADGRV1, KCNA2, KCNT1, KCNQ2, NPRL3, PCDH19, RHOBTB2, SCN9A, and SLC2A1.
Drug-resistant epilepsy [p=0.008, 95% CI 6.2 (1.6-19.4)] and ≥5 seizures in infancy [p=0.042, 95%CI 3.5 (1.1-11.9)] were found to be significant predictor of genetic pathogenicity. The presence of pathogenic variants was also significantly associated with adverse neurodevelopment [p=0.009 95% CI 5.2 (1.5-15.8)].
Conclusions: Our study provides proof-of-concept of underlying genetic etiology in children with DTP vaccination associated seizures and subsequent epilepsy. We highlight the genetic heterogeneity of DTP vaccine associated seizures/epilepsy with 15 genes and 17 novel implicated genetic variants.
Funding: Please list any funding that was received in support of this abstract.: International Pediatric Association Foundation, Inc. (IPAF); Indian Council of Medical Research (ICMR), New Delhi.
Genetics