Mutations in the Δ7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome

Barbara U. Fitzky, Martina Witsch-Baumgartner, Martin Erdel, Joon No Lee, Young Ki Paik, Hartmut Glossmann, Gerd Utermann, Fabian F. Moebius

Research output: Contribution to journalArticle

298 Citations (Scopus)

Abstract

The Smith-Lemli-Opitz syndrome (SLOS) is an inborn disorder of sterol metabolism with characteristic congenital malformations and dysmorphias. All patients suffer from mental retardation. Here we identify the SLOS gene as a Δ7-sterol reductase (DHCR7, EC 1.3.1.21) required for the de novo biosynthesis of cholesterol. The human and murine genes were characterized and assigned to syntenic regions on chromosomes 11q13 and 7F5 by fluorescense in situ hybridization. Among the mutations found in patients with the SLOS, are missense (P51S, T93M, L99P, L157P, A247V, V326L, R352W, C380S, R404C, and G410S), nonsense (W151X), and splice site (IVS8-1G>C) mutations as well as an out of frame deletion (720-735 del). The missense mutations L99P, V326L, R352W, R404C, and G410S reduced heterologous protein expression by >90%. Our results strongly suggest that defects in the DHCR7 gene cause the SLOS.

Original languageEnglish
Pages (from-to)8181-8186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number14
DOIs
Publication statusPublished - 1998 Jul 7

Fingerprint

Smith-Lemli-Opitz Syndrome
Sterols
Oxidoreductases
Mutation
Genes
Frameshift Mutation
Missense Mutation
Intellectual Disability
In Situ Hybridization
Chromosomes
Cholesterol
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Fitzky, Barbara U. ; Witsch-Baumgartner, Martina ; Erdel, Martin ; Lee, Joon No ; Paik, Young Ki ; Glossmann, Hartmut ; Utermann, Gerd ; Moebius, Fabian F. / Mutations in the Δ7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 14. pp. 8181-8186.
@article{426bf1d182c54b3cbb809d33c3d8b414,
title = "Mutations in the Δ7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome",
abstract = "The Smith-Lemli-Opitz syndrome (SLOS) is an inborn disorder of sterol metabolism with characteristic congenital malformations and dysmorphias. All patients suffer from mental retardation. Here we identify the SLOS gene as a Δ7-sterol reductase (DHCR7, EC 1.3.1.21) required for the de novo biosynthesis of cholesterol. The human and murine genes were characterized and assigned to syntenic regions on chromosomes 11q13 and 7F5 by fluorescense in situ hybridization. Among the mutations found in patients with the SLOS, are missense (P51S, T93M, L99P, L157P, A247V, V326L, R352W, C380S, R404C, and G410S), nonsense (W151X), and splice site (IVS8-1G>C) mutations as well as an out of frame deletion (720-735 del). The missense mutations L99P, V326L, R352W, R404C, and G410S reduced heterologous protein expression by >90{\%}. Our results strongly suggest that defects in the DHCR7 gene cause the SLOS.",
author = "Fitzky, {Barbara U.} and Martina Witsch-Baumgartner and Martin Erdel and Lee, {Joon No} and Paik, {Young Ki} and Hartmut Glossmann and Gerd Utermann and Moebius, {Fabian F.}",
year = "1998",
month = "7",
day = "7",
doi = "10.1073/pnas.95.14.8181",
language = "English",
volume = "95",
pages = "8181--8186",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "14",

}

Mutations in the Δ7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. / Fitzky, Barbara U.; Witsch-Baumgartner, Martina; Erdel, Martin; Lee, Joon No; Paik, Young Ki; Glossmann, Hartmut; Utermann, Gerd; Moebius, Fabian F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 14, 07.07.1998, p. 8181-8186.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mutations in the Δ7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome

AU - Fitzky, Barbara U.

AU - Witsch-Baumgartner, Martina

AU - Erdel, Martin

AU - Lee, Joon No

AU - Paik, Young Ki

AU - Glossmann, Hartmut

AU - Utermann, Gerd

AU - Moebius, Fabian F.

PY - 1998/7/7

Y1 - 1998/7/7

N2 - The Smith-Lemli-Opitz syndrome (SLOS) is an inborn disorder of sterol metabolism with characteristic congenital malformations and dysmorphias. All patients suffer from mental retardation. Here we identify the SLOS gene as a Δ7-sterol reductase (DHCR7, EC 1.3.1.21) required for the de novo biosynthesis of cholesterol. The human and murine genes were characterized and assigned to syntenic regions on chromosomes 11q13 and 7F5 by fluorescense in situ hybridization. Among the mutations found in patients with the SLOS, are missense (P51S, T93M, L99P, L157P, A247V, V326L, R352W, C380S, R404C, and G410S), nonsense (W151X), and splice site (IVS8-1G>C) mutations as well as an out of frame deletion (720-735 del). The missense mutations L99P, V326L, R352W, R404C, and G410S reduced heterologous protein expression by >90%. Our results strongly suggest that defects in the DHCR7 gene cause the SLOS.

AB - The Smith-Lemli-Opitz syndrome (SLOS) is an inborn disorder of sterol metabolism with characteristic congenital malformations and dysmorphias. All patients suffer from mental retardation. Here we identify the SLOS gene as a Δ7-sterol reductase (DHCR7, EC 1.3.1.21) required for the de novo biosynthesis of cholesterol. The human and murine genes were characterized and assigned to syntenic regions on chromosomes 11q13 and 7F5 by fluorescense in situ hybridization. Among the mutations found in patients with the SLOS, are missense (P51S, T93M, L99P, L157P, A247V, V326L, R352W, C380S, R404C, and G410S), nonsense (W151X), and splice site (IVS8-1G>C) mutations as well as an out of frame deletion (720-735 del). The missense mutations L99P, V326L, R352W, R404C, and G410S reduced heterologous protein expression by >90%. Our results strongly suggest that defects in the DHCR7 gene cause the SLOS.

UR - http://www.scopus.com/inward/record.url?scp=0032493196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032493196&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.14.8181

DO - 10.1073/pnas.95.14.8181

M3 - Article

C2 - 9653161

AN - SCOPUS:0032493196

VL - 95

SP - 8181

EP - 8186

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -