Journal of The Korean Society of Inherited Metabolic disease (대한유전성대사질환학회지)

The Korea Society of Inherited Metabolic Disease (대한유전성대사질환학회)
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Vici Syndrome with Novel Compound Heterozygous Mutations in EPG5

EPG5 유전자 변이가 확인된 Vici 증후군 1례

  • Shin, Jehee (Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Lee, Hyunjoo (Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Lee, Young-Mock (Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine)
  • 신제희 (연세대학교 의과대학 강남세브란스병원 소아청소년과) ;
  • 이현주 (연세대학교 의과대학 강남세브란스병원 소아청소년과) ;
  • 이영목 (연세대학교 의과대학 강남세브란스병원 소아청소년과)
  • Published : 2020.12.31
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Abstract

Vici syndrome is a rare, autosomal recessive multisystem disorder characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, hypopigmentation, immunodeficiency, and delayed development. We report the case of a 3-year-old boy diagnosed with Vici syndrome. He initially presented with hypotonia and sucking problem. Whole-exome sequencing identified novel compound heterozygous mutations, namely c.2254C>T (p.Gln752Ter) and c.5511-5518+2 del TATGCAAAGT in the EPG5 gene. The diagnostic challenges can be attributed to the diverse clinical manifestations. Thus, whole-exome sequencing is a useful diagnostic tool for the genetically and clinically heterogeneous Vici syndrome. This is the first Korean report of a patient with Vici syndrome.

Vici 증후군은 18q12.3 염색체에 위치하는 EPG5 유전자의 돌연변이로 인해 발생하는 상 염색체 열성 증후군이다. EPG5 유전자는 리소좀 형성에 관여하는 자가 포식 경로의 중요한 조절자를 암호화하므로 이에 대한 돌연변이로 인해 다양한 임상증상을 나타나게 된다. 주요한 임상증상으로는 뇌량 무형성, 백색증, 백내장, 심근 병증, 중증 정신 운동 지체, 발작, 면역 결핍 등이 있으며 다양한 임상증상을 나타내는 만큼 다른 질환들과 임상적으로 구분하기가 어렵다. 저자들은 Vici 증후군으로 진단된 3세 남자 환아의 증례를 보고하고자 한다. 환아는 생후 2개월 경 근긴장 저하와 수유 곤란을 주소로 내원하였으며 이후 Vici 증후군에서 나타나는 특징적인 임상 증상들을 나타내었다. 임상증상들의 감별 진단을 위해 시행한 Whole-exome sequencing (WES) 결과, EPG5 유전자에서 c.2254 C>T (p.Gln752Ter)와 c.5511-5518+2 del TATGCAAAGT 새로운 변이가 이형접합체로 확인되었다. Vici 증후군과 같이 임상적으로 구분이 어려우며 다양한 신체기관에 걸쳐 영향을 미치는 질환의 진단 시에는 Whole-exome sequencing (WES)가 유용하게 사용될 수 있다. 이 증례는 한국에서 확인된 첫 Vici 증후군 case로써 의의가 있다.

Keywords

References

  1. Moirangthem A, Mandal K, Ghosh A, Phadke SR. Vici syndrome with a novel mutation in EPG5. Indian Pediatr 2019;56:603-5. https://doi.org/10.1007/s13312-019-1561-z
  2. Finicch A, Angelino G, Cantarutti N, Corbari M, Bevivino E, Cascioli S, et al. Immunodeficiency in Vici syndrome: A heterogenous phenotype. Am J Med Genet 2012;158:434-9.
  3. Byrne S, Doinisi-Vici C, Smith L, Gautel M, Junebluth H. Vici syndrom: a review. Orphanet J Rare Dis 2016;11:1-9. https://doi.org/10.1186/s13023-016-0515-y
  4. Cullup T, Kho AL, Dionisi-Vici C, Brandmeier B, Smith F, Urry Z, et al. Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy. Nature Genet 2013;45:83-7. https://doi.org/10.1038/ng.2497
  5. Balasubramaniam S, Riley LG, Vasudevan A, Cowley MJ, Gayevskiy V, Sue CM, et al. EPG5-related Vici syndrome: A primary defect of autophagic regulatation with an emerging phenotype overlapping with mitochondrial disorders. J Inherit Metab Dis 2017;42:19-29.
  6. Byrne S, Jansen L, U-King-Im JM, Siddiqui A, Lidov HG, Bodi I, et al. EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy. Brain 2016;139;765-81. https://doi.org/10.1093/brain/awv393
  7. Demiral E, Sen A, Esener Z, Ceylaner S, Tekedereli I. A rare mutation in the EPG5 gene causes Vici syndrome. Clin Dysmorphol 2018:27:145-7. https://doi.org/10.1097/mcd.0000000000000233
  8. Alzahrani A, Alghamdi AA, Waggass R. A Saudi infant with vici syndrome: case report and literature review. Open Access Maced J Med Sci 2019;6:1081-4. https://doi.org/10.3889/oamjms.2018.271
  9. Mortari PE, Folgiero V, Marcellini V, Romania P, Bellacchio E, D'Alicandro, V, et al. The Vici syndrome protein EPG5 regulates intracellular nucleic acid trafficking linking autophagy to innate and adaptive immunity. Autophagy 2018;1422-37.
  10. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015:17:405-24. https://doi.org/10.1038/gim.2015.30
  11. Miyata R, Hayashi M, Itoh E. Pathological changes in cardiac muscle and cerebellar cortex in Vici syndrome. Am J Med Genet A 2014;164:3203-5. https://doi.org/10.1002/ajmg.a.36753
  12. Jokl, E J ,Blanco G. Disrupted autophagy undermines skeletal muscle adaptation and integrity. Mammalian Genome 2016;27:525-37. https://doi.org/10.1007/s00335-016-9659-2