Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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A case of Smith-Lemli-Opitz syndrome confirmed by molecular analysis: Review of mutation spectrum of the DHCR7 gene in Korea

  • Oh, Moon-Yeon (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Kim, Jun Suk (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Kim, Ja Hye (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Cho, Ja Hyang (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Lee, Beom Hee (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Kim, Gu-Hwan (Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Choi, Jin-Ho (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine)
  • Received : 2014.08.21
  • Accepted : 2014.09.27
  • Published : 2014.12.31
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Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a rare autosomal recessive disorder caused by 7-dehydrocholesterol reductase deficiency. The characteristic clinical features are syndactyly of the second and third toes, facial dysmorphism, multiple malformations, and intellectual disability. Few cases of SLOS have been reported in Korea. We observed a male patient with SLOS who presented with typical facial features, undescended testes, microcephaly, bilateral syndactyly of the second and third toes, and cardiac defects, including patent ductus arteriosus and atrial septal defect. Mutation analysis of the DHCR7 gene identified compound heterozygous mutations of c.907G>A (p.Gly303Arg) and c.1055G>A (p.Arg352Gln). In a review of the literature, c.1054C>T (p.Arg352Trp) was the most common mutation reported in Far East Asian countries. This report describes the clinical features, biochemical data, molecular characteristics, and clinical outcome of a Korean patient with SLOS.

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References

  1. Nowaczyk MJ, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet 2012;160C:250-62. https://doi.org/10.1002/ajmg.c.31343
  2. Smith DW, Lemli L, Opitz JM. A newly recognized syndrome of multiple congenital anomalies. J Pediatr 1964;64:210-7. https://doi.org/10.1016/S0022-3476(64)80264-X
  3. Kelley RI, Hennekam RC. The Smith-Lemli-Opitz syndrome. J Med Genet 2000;37:321-35. https://doi.org/10.1136/jmg.37.5.321
  4. Porter FD. RSH/Smith-Lemli-Opitz syndrome: a multiple congenital anomaly/mental retardation syndrome due to an inborn error of cholesterol biosynthesis. Mol Genet Metab 2000;71:163-74. https://doi.org/10.1006/mgme.2000.3069
  5. Kelley RI. Diagnosis of Smith-Lemli-Opitz syndrome by gas chromatography/mass spectrometry of 7-dehydrocholesterol in plasma, amniotic fluid and cultured skin fibroblasts. Clin Chim Acta 1995;236:45-58. https://doi.org/10.1016/0009-8981(95)06038-4
  6. Fitzky BU, Witsch-Baumgartner M, Erdel M, Lee JN, Paik YK, Glossmann H, et al. Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. Proc Natl Acad Sci U S A 1998;95:8181-6. https://doi.org/10.1073/pnas.95.14.8181
  7. Ko JS, Choi BS, Seo JK, Shin JY, Chae JH, Kang GH, et al. A novel DHCR7 mutation in a Smith-Lemli-Opitz syndrome infant presenting with neonatal cholestasis. J Korean Med Sci 2010;25:159-62. https://doi.org/10.3346/jkms.2010.25.1.159
  8. Lee HJ, Lee JH, Lee JS, Choe YH. The Smith-Lemli-Opitz syndrome with a G303R/R352W mutation: in an extremely irritable child responsive to cholesterol supplementation. Genes Genomic 2010;32:9-12. https://doi.org/10.1007/s13258-010-0687-0
  9. Park MR, Ko JM, Cheon CK, Kim GH, Yoo HW. A case of Smith-Lemli- Opitz syndrome diagnosed by identification of mutations in the 7-dehydrocholesterol reductase (DHCR7) gene. Korean J Pediatr 2008;51:1236-40. https://doi.org/10.3345/kjp.2008.51.11.1236
  10. Chae JH, Kim KJ, Hwang YS, Ki CS, Kim JW. Identification of a novel DHCR7 mutation in a Korean patient with Smith-Lemli-Opitz syndrome. J Child Neurol 2007;22:1297-300. https://doi.org/10.1177/0883073807307099
  11. Ko JM. Clinical and molecular genetic characteristics of Korean patients with Smith-Lemli-Opitz syndrome: a report of new patients with a literature review. J Korean Soc Inher Metab Dis 2014;14:48-53.
  12. Jeong YJ, Huh R, Kwun YH, Lee JE, Cho SY, Ki CS, et al. A case of Smith-Lemli-Opitz syndrome in DHCR7 mutation. J Korean Soc Inher Metab Dis 2014;14:60-65.
  13. Matsumoto Y, Morishima K, Honda A, Watabe S, Yamamoto M, Hara M, et al. R352Q mutation of the DHCR7 gene is common among Japanese Smith-Lemli-Opitz syndrome patients. J Hum Genet 2005;50:353-6. https://doi.org/10.1007/s10038-005-0267-3
  14. Tint GS, Irons M, Elias ER, Batta AK, Frieden R, Chen TS, et al. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med 1994;330:107-13. https://doi.org/10.1056/NEJM199401133300205
  15. Witsch-Baumgartner M, Löffler J, Utermann G. Mutations in the human DHCR7 gene. Hum Mutat 2001;17:172-82. https://doi.org/10.1002/humu.2
  16. Waterham HR, Hennekam RC. Mutational spectrum of Smith- Lemli-Opitz syndrome. Am J Med Genet C Semin Med Genet 2012;160C:263-84. https://doi.org/10.1002/ajmg.c.31346
  17. Yu H, Tint GS, Salen G, Patel SB. Detection of a common mutation in the RSH or Smith-Lemli-Opitz syndrome by a PCR-RFLP assay: IVS8- G-->C is found in over sixty percent of US propositi. Am J Med Genet 2000;90:347-50. https://doi.org/10.1002/(SICI)1096-8628(20000214)90:4<347::AID-AJMG16>3.0.CO;2-7
  18. Jira PE, Waterham HR, Wanders RJ, Smeitink JA, Sengers RC, Wevers RA. Smith-Lemli-Opitz syndrome and the DHCR7 gene. Ann Hum Genet 2003;67:269-80. https://doi.org/10.1046/j.1469-1809.2003.00034.x
  19. Svoboda MD, Christie JM, Eroglu Y, Freeman KA, Steiner RD. Treatment of Smith-Lemli-Opitz syndrome and other sterol disorders. Am J Med Genet C Semin Med Genet 2012;160C:285-94. https://doi.org/10.1002/ajmg.c.31347
  20. Abuelo DN, Tint GS, Kelley R, Batta AK, Shefer S, Salen G. Prenatal detection of the cholesterol biosynthetic defect in the Smith-Lemli- Opitz syndrome by the analysis of amniotic fluid sterols. Am J Med Genet 1995;56:281-5. https://doi.org/10.1002/ajmg.1320560309