scholarly journals Smith–Lemli–Opitz Mutations in Unexplained Stillbirths

2018 ◽  
Vol 35 (10) ◽  
pp. 936-939 ◽  
Author(s):  
Uma Reddy ◽  
George Saade ◽  
Robert Goldenberg ◽  
Donald Dudley ◽  
Corette Parker ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cholesterol Biosynthesis ◽  
Strong Association ◽  
Placental Tissue ◽  
Population Based ◽  
Poor Quality ◽  
Single Mutation ◽  
Live Births ◽  
Opitz Syndrome ◽  
Control Study

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.

scholarly journals A koleszterin-bioszintézis veleszületett zavara: a Smith–Lemli–Opitz-szindróma

2015 ◽  
Vol 156 (42) ◽  
pp. 1695-1702
Author(s):  
Katalin Koczok ◽  
Anna V. Oláh ◽  
Gabriella P. Szabó ◽  
Éva Oláh ◽  
Olga Török ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Concentration ◽  
Common Symptom ◽  
Incidence Data ◽  
Serum Cholesterol Concentration ◽  
Multiple Malformation ◽  
Opitz Syndrome ◽  
Cholesterol Supplementation ◽  
Diagnostics And Therapy

Smith–Lemli–Opitz syndrome is an autosomal recessive mental retardation and multiple malformation syndrome caused by deficiency of the 7-dehydrocholesterol reductase, the enzyme catalyzing the last step in cholesterol biosynthesis. The authors summarize the pathophysiology, epidemiology, clinical picture, diagnostics and therapy of the disease based on a review of the international literature. Since 2004, fourteen patients have been diagnosed with Smith–Lemli–Opitz syndrome in Hungary, which suggests an underdiagnosis of the disease based upon estimated incidence data. Due to deficiency of the 7-dehydrocholesterol reductase, serum cholesterol concentration is low and 7-dehydrocholesterol concentration is elevated in blood and tissues; the latter being highly specific for the syndrome. Detection of disease-causing mutations makes the prenatal diagnosis possible. The clinical spectrum is wide, the most common symptom is syndactyly of the second and third toes. Standard therapy is cholesterol supplementation. Recent publications suggest that oxidative compounds of 7-dehydrocholesterol may play a role in the pathophysiology of the disease as well. Orv. Hetil., 2015, 156(42), 1695–1702.

scholarly journals Sarcoma of the breast: breast cancer history as etiologic and prognostic factor—A population-based case–control study

2020 ◽  
Vol 183 (3) ◽  
pp. 669-675 ◽  
Author(s):  
Fredrik Karlsson ◽  
Fredrik Granath ◽  
Karin E. Smedby ◽  
Jan Zedenius ◽  
Robert Bränström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Strong Association ◽  
Population Based ◽  
Mesenchymal Tumors ◽  
Cancer History ◽  
Angiosarcoma Of The Breast ◽  
History Of ◽  
And Gender ◽  
Breast Breast Cancer ◽  
Control Study

Abstract Purpose Sarcomas of the breast account for about 1% of all breast malignancies. The aim of this national survey was to explore etiologic and prognostic factors. Methods Utilizing national Swedish registers, all patients registered with mesenchymal tumors in the breast during the period 1993–2013 (n = 344) were identified and compared to up to ten age and gender matched controls. Cancer history was retrieved for cases and controls. Conditional Poisson regression models were used for calculation of odds ratios. Results Previous breast cancer was overrepresented among patients with angiosarcoma. The highest risk occurred ≥ 5 years after treatment for breast cancer (OR 73.9, 95% confidence interval, CI, 25.4–215; P < 0.001). An increase in incidence of angiosarcoma was observed during the study period (1.10, 95% CI 1.05–1.16; P < 0.001). The overall incidence of breast sarcoma increased from 1.52 to 2.04 cases per million per year. Angiosarcoma of the breast was associated with a significant excess mortality compared to age-matched controls (HR 4.65, 95% CI 3.01–7.19; P < 0.001). Conclusions Angiosarcoma increased in incidence and displayed a more severe clinical course, with significantly shorter survival. The strong association between a history of breast cancer 5 years or more prior to the diagnosis of angiosarcoma points to radiotherapy as a contributing factor.

535: Population-Based Case-Control Study of PSA and DRE Screening on Prostate Cancer Mortality

2005 ◽  
Vol 173 (4S) ◽  
pp. 146-146
Author(s):  
Eric J. Bergstralh ◽  
Rosebud O. Roberts ◽  
Michael M. Lieber ◽  
Sara A. Farmer ◽  
Jeffrey M. Slezak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Mortality ◽  
Case Control Study ◽  
Population Based ◽  
Case Control ◽  
Prostate Cancer Mortality ◽  
Control Study

HLA Genotype of Patients with Severe Haemophilia A due to Intron 22 Inversion with and without Inhibitors of Factor VIII

1997 ◽  
Vol 77 (02) ◽  
pp. 238-242 ◽  
Author(s):  
J Oldenburg ◽  
J K Picard ◽  
R Schwaab ◽  
H H Brackmann ◽  
E G D Tuddenham ◽  
...  
Keyword(s):  
Factor Viii ◽  
Major Gene ◽  
Statistical Significance ◽  
Strong Association ◽  
Molecular Genetic ◽  
Single Mutation ◽  
Severe Haemophilia ◽  
Extended Haplotype ◽  
Intron 22 Inversion ◽  
Hla Genotype

SummaryMolecular genetic studies have shown that development of antibodies to factor VIII (inhibitors) occurs most frequently in patients with severe haemophilia due to major gene lesions including inversions, stop codons and large deletions. Previous studies of HLA type were performed on inhibitor and non-inhibitor patients with diverse uncharacterised mutations which may have confounded detection of significant associations. We therefore selected a group of patients with a single mutation type, the prevalent intron 22 inversion, with or without inhibitors, to determine HLA genotype. Seventy-one such patients, 42 without and 29 with inhibitors (13 high, 9 low and 7 transient responders) were genotyped for MHC Class I HLA-A, -B, -C and Class II HLA-DQA, -DQB and -DRB loci. No strong correlation of any HLA-allele to inhibitor or non-inhibitor status was found. However, alleles of the haplotype HLA-A3, HLA-B7, HLA-C7, HLA-DQA0102, HLA-DQB0602, HLA-DR15 occurred more often in inhibitor patients. Since the alleles of this extended haplotype are common in the North European population only a very strong association would achieve statistical significance. Further studies of groups of patients similar to those studied here will be needed to confirm or exclude this association.

Gene-diet interactions in the aetiology of colorectal cancer: results from a population-based case-control study in north-east Scotland

Endoscopy ◽  
2006 ◽  
Vol 37 (12) ◽  
Author(s):  
L Sharp ◽  
LF Masson ◽  
J Little ◽  
NT Brockton ◽  
SC Cotton ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Control Study ◽  
Population Based ◽  
Case Control ◽  
North East ◽  
Control Study
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