title: SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism.
abstract: BACKGROUND
  Genetic mutations play a crucial role in the etiology of cryptogenic infantile spasms, but the cause is still unknown in a significant proportion of patients. Whole exome sequencing technology shows great promise in identifying genetic causes of infantile spasms.
  
  
  METHODS
  In this study whole exome sequencing was performed with 2-deoxy-2-((18)F)fluoro-d-glucose positron emission tomography scan of an infant boy with infantile spasms. Exome sequencing was also performed in the parents to identify any de novo mutations.
  
  
  RESULTS
  The positron emission tomography scan showed a pattern of bilateral symmetric temporal lobe glucose hypometabolism. A total of 8171 nonsynonymous variants were identified in the child. Despite the large number of nonsynonymous variants, there was only a single de novo missense mutation in SCN2A in the child (NCBI hg19 assembly, position: Chr2:166234116, K1422E). Subsequent Sanger sequencing confirmed the de novo status of this variant. This mutation has never been reported in 6500 individuals of the exome variant server database. Similarly, this variant is not reported in the Online Mendelian Inheritance in Man Database or the Human Gene Mutation Database. It has previously been shown that SCN2A mutations are associated with hippocampal hyperexcitability. Therefore, this study indicates that infantile spasms and bitemporal hypometabolism in this patient might have been caused by hippocampal hyperexcitability due to SCN2A mutation.
  
  
  CONCLUSIONS
  The simultaneous presence of an SCN2A mutation and bitemporal hypometabolism in this patient with infantile spasms suggests a plausible hippocampal origin. However, additional mechanistic and clinical studies are required to validate this link.
authors.affiliation: Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, MI, USA.
authors.forename: Senthil K
authors.initials: SK
authors.lastname: Sundaram
authors.forename: Harry T
authors.initials: HT
authors.lastname: Chugani
authors.forename: Vijay N
authors.initials: VN
authors.lastname: Tiwari
authors.forename: A H M M
authors.initials: AH
authors.lastname: Huq
mesh_terms: D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics*; D011877:Radionuclide Imaging; D013036:Spasms, Infantile / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; C568251:SCN2A protein, human; D005947:Glucose