Smith-Lemli-Opitz Mutations in Unexplained Stillbirths

Karen Gibbins, Uma M. Reddy, George R. Saade, Robert L. Goldenberg, Donald J. Dudley, Corette B. Parker, Vanessa Thorsten, Halit Pinar, Radek Bukowski, Carol J. Hogue, Robert M. Silver

Research output: Contribution to journalArticle

Abstract

Objective Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by a defect in cholesterol biosynthesis with mutations in 7-dehydrocholesterol reductase (DHCR7). A total of 3% of Caucasians carry DHCR7 mutations, theoretically resulting in a homozygote frequency of 1/4000. However, SLOS occurs in only 1/20,000 to 60,000 live births. Our objective was to assess DHCR7 mutations in unexplained stillbirths. Study Design Prospective, multicenter, population-based case-control study of all stillbirths and a representative sample of live births enrolled in five geographic areas. Cases with stillbirth due to obstetric complications, infection, or aneuploidy, and those with poor quality deoxyribonucleic acid (DNA) were excluded. DNA was extracted from placental tissue stored at -80°C, and exons 3 to 9 of the DCHR7 gene were amplified, purified, and subjected to bidirectional sequencing to identify mutations. Results One-hundred forty four stillbirths were unexplained and had adequate DNA for analysis. Nine stillbirths of 139 (6.5%) had a single mutation in one allele in coding exons 3 to 9 of DHCR7 (Table 1). One case (0.7%) was a compound heterozygote for mutations in exons 3 to 9 of DHCR7; this fetus had no clinical or histologic features of SLOS. Conclusion We detected SLOS mutations in only 0.7% of stillbirths. This does not support a strong association between unrecognized DHCR7 mutations and stillbirth.

Original languageEnglish (US)
Pages (from-to)936-939
Number of pages4
JournalAmerican Journal of Perinatology
Volume35
Issue number10
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

Fingerprint

Stillbirth
Smith-Lemli-Opitz Syndrome
Mutation
Exons
Live Birth
DNA
Homozygote
Aneuploidy
Heterozygote
Obstetrics
Case-Control Studies
Fetus
Alleles
Cholesterol
Prospective Studies
Infection

Keywords

  • cholesterol biosynthesis
  • genetic syndrome
  • Smith-Lemli-Opitz
  • stillbirth

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Gibbins, K., Reddy, U. M., Saade, G. R., Goldenberg, R. L., Dudley, D. J., Parker, C. B., ... Silver, R. M. (2018). Smith-Lemli-Opitz Mutations in Unexplained Stillbirths. American Journal of Perinatology, 35(10), 936-939. https://doi.org/10.1055/s-0038-1626705

Smith-Lemli-Opitz Mutations in Unexplained Stillbirths. / Gibbins, Karen; Reddy, Uma M.; Saade, George R.; Goldenberg, Robert L.; Dudley, Donald J.; Parker, Corette B.; Thorsten, Vanessa; Pinar, Halit; Bukowski, Radek; Hogue, Carol J.; Silver, Robert M.

In: American Journal of Perinatology, Vol. 35, No. 10, 01.08.2018, p. 936-939.

Research output: Contribution to journalArticle

Gibbins, K, Reddy, UM, Saade, GR, Goldenberg, RL, Dudley, DJ, Parker, CB, Thorsten, V, Pinar, H, Bukowski, R, Hogue, CJ & Silver, RM 2018, 'Smith-Lemli-Opitz Mutations in Unexplained Stillbirths', American Journal of Perinatology, vol. 35, no. 10, pp. 936-939. https://doi.org/10.1055/s-0038-1626705
Gibbins K, Reddy UM, Saade GR, Goldenberg RL, Dudley DJ, Parker CB et al. Smith-Lemli-Opitz Mutations in Unexplained Stillbirths. American Journal of Perinatology. 2018 Aug 1;35(10):936-939. https://doi.org/10.1055/s-0038-1626705
Gibbins, Karen ; Reddy, Uma M. ; Saade, George R. ; Goldenberg, Robert L. ; Dudley, Donald J. ; Parker, Corette B. ; Thorsten, Vanessa ; Pinar, Halit ; Bukowski, Radek ; Hogue, Carol J. ; Silver, Robert M. / Smith-Lemli-Opitz Mutations in Unexplained Stillbirths. In: American Journal of Perinatology. 2018 ; Vol. 35, No. 10. pp. 936-939.
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abstract = "Objective Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by a defect in cholesterol biosynthesis with mutations in 7-dehydrocholesterol reductase (DHCR7). A total of 3{\%} of Caucasians carry DHCR7 mutations, theoretically resulting in a homozygote frequency of 1/4000. However, SLOS occurs in only 1/20,000 to 60,000 live births. Our objective was to assess DHCR7 mutations in unexplained stillbirths. Study Design Prospective, multicenter, population-based case-control study of all stillbirths and a representative sample of live births enrolled in five geographic areas. Cases with stillbirth due to obstetric complications, infection, or aneuploidy, and those with poor quality deoxyribonucleic acid (DNA) were excluded. DNA was extracted from placental tissue stored at -80°C, and exons 3 to 9 of the DCHR7 gene were amplified, purified, and subjected to bidirectional sequencing to identify mutations. Results One-hundred forty four stillbirths were unexplained and had adequate DNA for analysis. Nine stillbirths of 139 (6.5{\%}) had a single mutation in one allele in coding exons 3 to 9 of DHCR7 (Table 1). One case (0.7{\%}) was a compound heterozygote for mutations in exons 3 to 9 of DHCR7; this fetus had no clinical or histologic features of SLOS. Conclusion We detected SLOS mutations in only 0.7{\%} of stillbirths. This does not support a strong association between unrecognized DHCR7 mutations and stillbirth.",
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AU - Dudley, Donald J.

AU - Parker, Corette B.

AU - Thorsten, Vanessa

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N2 - Objective Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by a defect in cholesterol biosynthesis with mutations in 7-dehydrocholesterol reductase (DHCR7). A total of 3% of Caucasians carry DHCR7 mutations, theoretically resulting in a homozygote frequency of 1/4000. However, SLOS occurs in only 1/20,000 to 60,000 live births. Our objective was to assess DHCR7 mutations in unexplained stillbirths. Study Design Prospective, multicenter, population-based case-control study of all stillbirths and a representative sample of live births enrolled in five geographic areas. Cases with stillbirth due to obstetric complications, infection, or aneuploidy, and those with poor quality deoxyribonucleic acid (DNA) were excluded. DNA was extracted from placental tissue stored at -80°C, and exons 3 to 9 of the DCHR7 gene were amplified, purified, and subjected to bidirectional sequencing to identify mutations. Results One-hundred forty four stillbirths were unexplained and had adequate DNA for analysis. Nine stillbirths of 139 (6.5%) had a single mutation in one allele in coding exons 3 to 9 of DHCR7 (Table 1). One case (0.7%) was a compound heterozygote for mutations in exons 3 to 9 of DHCR7; this fetus had no clinical or histologic features of SLOS. Conclusion We detected SLOS mutations in only 0.7% of stillbirths. This does not support a strong association between unrecognized DHCR7 mutations and stillbirth.

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