Smith–Lemli–Opitz Mutations in Unexplained Stillbirths

Karen J. 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

doi:10.1055/s-0038-1626705

American Journal of Perinatology, Table of Contents

Am J Perinatol 2018; 35(10): 936-939
DOI: 10.1055/s-0038-1626705

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Smith–Lemli–Opitz Mutations in Unexplained Stillbirths

Karen J. Gibbins

¹Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah

,

Uma M. Reddy

²Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland

,

George R. Saade

³Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas

,

Robert L. Goldenberg

⁴Department of Obstetrics and Gynecology, Columbia University School of Medicine, New York, New York

,

Donald J. Dudley

⁵Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, Virginia

,

Corette B. Parker

⁶RTI International, Durham, North Carolina

,

Vanessa Thorsten

⁶RTI International, Durham, North Carolina

,

Halit Pinar

⁷Department of Pediatric and Developmental Pathology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island

,

Radek Bukowski

⁸Department of Women's Health, University of Texas–Austin, Austin, Texas

,

Carol J. Hogue

⁹Department of Epidemiology, Emory University, Atlanta, Georgia

,

Robert M. Silver

¹Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah

› Author Affiliations

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.

Keywords

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

Full Text

References

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