Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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A case of Galloway-Mowat syndrome with novel compound heterozygous variants in the WDR4 gene

  • Kim, Hamin (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)
  • Received : 2020.09.15
  • Accepted : 2020.10.29
  • Published : 2020.12.31
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Abstract

The combination of central nervous system abnormalities and renal impairment is a notable characteristic of Galloway-Mowat syndrome (GAMOS), a disease which often accompanies microcephaly, developmental delay, and nephrotic syndrome. Many subtypes exist having various phenotypes and genotypes, and many genetic causes are still being identified. An 18-month-old boy first visited our clinic for seizure, delayed development, and microcephaly. During follow-up visits he developed proteinuria and nephrotic syndrome at the age of 6. Nephrotic syndrome became refractory to treatment. These phenotypes were suggestive of GAMOS. Next generation sequencing was performed for genetic analysis and revealed novel compound heterozygous variants in the WDR4 gene: c.494G>A (p.Arg165Gln) and c.540C>G (p.Ile180Met). This is the first case in Korea of GAMOS involving the WDR4 gene.

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References

  1. Galloway WH, Mowat AP. Congenital microcephaly with hiatus hernia and nephrotic syndrome in two sibs. J Med Genet 1968;5:319-21. https://doi.org/10.1136/jmg.5.4.319
  2. Colin E, Huynh Cong E, Mollet G, Guichet A, Gribouval O, Arrondel C, et al. Loss-of-function mutations in WDR73 are responsible for microcephaly and steroid-resistant nephrotic syndrome: GallowayMowat syndrome. Am J Hum Genet 2014;95:637-48. https://doi.org/10.1016/j.ajhg.2014.10.011
  3. El Younsi M, Kraoua L, Meddeb R, Ferjani M, Trabelsi M, Ouertani I, et al. WDR73-related Galloway Mowat syndrome with collapsing glomerulopathy. Eur J Med Genet 2019;62:103550. https://doi.org/10.1016/j.ejmg.2018.10.002
  4. Braun DA, Rao J, Mollet G, Schapiro D, Daugeron MC, Tan W, et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet 2017;49:1529-38. https://doi.org/10.1038/ng.3933
  5. Braun DA, Shril S, Sinha A, Schneider R, Tan W, Ashraf S, et al. Mutations in WDR4 as a new cause of Galloway-Mowat syndrome. Am J Med Genet A 2018;176:2460-5. https://doi.org/10.1002/ajmg.a.40489
  6. Trimouille A, Lasseaux E, Barat P, Deiller C, Drunat S, Rooryck C, et al. Further delineation of the phenotype caused by biallelic variants in the WDR4 gene. Clin Genet 2018;93:374-7. https://doi.org/10.1111/cge.13074
  7. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al.; ACMG Laboratory Quality Assurance Committee. 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
  8. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010;7:248-9. https://doi.org/10.1038/nmeth0410-248
  9. Ekstrand JJ, Friedman AL, Stafstrom CE. Galloway-Mowat syndrome: neurologic features in two sibling pairs. Pediatr Neurol 2012;47:129-32. https://doi.org/10.1016/j.pediatrneurol.2012.04.011
  10. Cohen AH, Turner MC. Kidney in Galloway-Mowat syndrome: clinical spectrum with description of pathology. Kidney Int 1994;45:1407-15. https://doi.org/10.1038/ki.1994.184
  11. Alexandrov A, Martzen MR, Phizicky EM. Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. RNA 2002;8:1253-66. https://doi.org/10.1017/S1355838202024019
  12. Shaheen R, Abdel-Salam GM, Guy MP, Alomar R, Abdel-Hamid MS, Afifi HH, et al. Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism. Genome Biol 2015;16:210. https://doi.org/10.1186/s13059-015-0779-x