Estimation of the Carrier Frequency and Incidence of Smith-Lemli-Opitz Syndrome in African Americans

2014-08-27 03:56:50 | BioPortfolio


RSH/Smith-Lemli-Opitz syndrome (SLOS) is one that causes mental retardation. It is common in the Caucasian population but rare in African American and African black populations. It has been shown that SLOS is caused by a specific defect in DHCR7, an enzyme used in cholesterol metabolism. Studies have already been done to determine the frequency of the SLOS-causing mutations in various geographic Caucasian populations. This study will investigate the frequency of the DHCR7 mutations in the African American population. If the frequency observed suggests that SLOS cases are not being identified in this ethnic group, the study will provide the rationale for future studies to identify these patients.

The sample size will be 1,600. The study population will consist of archived biological specimens in the form of newborn screening blood spots from two newborn screening centers, one in Maryland and one in Pennsylvania. Subjects will be of African American ethnicity, including blacks of African, Caribbean, and Central American descent.

Genomic DNA will be extracted from blood spots and screened for the six common SLOS mutations. If SLOS syndrome is found, followup will be attempted for the Maryland samples (the Pennsylvania samples will be totally anonymous).


RSH/Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomaly/mental retardation syndrome caused by inborn error of cholesterol metabolism (Tint et al. 1994; Opitz 1999; Kelley 2000). Recent studies have shown SLOS to be one of the most common inherited metabolic defects in the Caucasian population. SLOS is believed to be rare in people of Chinese, Japanese, Indian, and Korean origin as well as in the African American and African Black population (Tsukahara et al. 1998; Yu et al 2000a; Witsch-Baumgartner et al. 2000; Witsch-Baumgartner et al. 2001, Battaile et al. 2001). The frequency spectra of DHCR7 mutations have been established for American Caucasians (Yu et al. 2000b, Battaile et al. 2001), mixed American Caucasian collection of patients (Witsch-Baumgartner et al 2000), for European ethnic groups from Poland, German/Austria, Great Britain (Witsch-Baumgartner et al. 2001) and from Italy (De Brasi et al. 1999). In these Caucasian populations, the most common mutations (IVS8-1G>C, W151X, V326L, R352W, R404C and T93M) account for 60% of SLOS mutant alleles. These suggest that frequent SLOS-causing mutations have different geographic origins and histories. This project will investigate the frequency gradient of DHCR7 mutations in the African American population.

Study Design



Smith-Lemli-Opitz Syndrome


National Institute of Child Health and Human Development (NICHD)
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:56:50-0400

Clinical Trials [915 Associated Clinical Trials listed on BioPortfolio]

Prenatal Screening For Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz Syndrome (SLOS) is a genetic condition that causes mental retardation and other birth defects. This study will evaluate a new prenatal screening test for SLOS.

Treatment of the Cholesterol Defect in Smith-Lemli-Opitz Syndrome

The purpose of this study is to determine whether supplementation with an oil-based cholesterol suspension will correct the biochemical abnormalities in cholesterol and its precursors in i...

Smith-Lemli-Opitz Syndrome and Cholic Acid

The purpose of this study is to determine whether dietary cholic acid therapy benefits people with Smith-Lemli-Opitz syndrome (SLOS) by leading to an increase in serum cholesterol and redu...

Phase II Study of Dietary Cholesterol for Smith-Lemli-Opitz Syndrome

OBJECTIVES: I. Examine the intestinal absorption of dietary cholesterol in patients with Smith-Lemli-Opitz syndrome. II. Measure the effect of dietary cholesterol on plasma sterol compo...

Short-term Behavioral Effects of Cholesterol Therapy in Smith-Lemli-Opitz Syndrome

This 10-week study will evaluate and compare behavior changes in children with Smith-Lemli-Opitz syndrome (SLOS) who are taking cholesterol supplementation versus those who are not on chol...

PubMed Articles [4806 Associated PubMed Articles listed on BioPortfolio]

The Smith-Lemli-Opitz syndrome and dentofacial anomalies diagnostic: Case reports and literature review.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder. It is due to a deficiency of 7-dehydrocholesterol reductase (DHCR7) that catalyses the reduction of 7-dehydrocholesterol (7-DHC) t...

Phenotypic description of two adult brothers presenting with mild form of Smith-Lemli-Opitz syndrome.

A female patient with X-linked Ohdo syndrome of the Maat-Kievit-Brunner phenotype caused by a novel variant of MED12.

MED12 is a component of the large multiprotein Mediator complex. MED12 variants have been linked to three different X-linked intellectual disability (ID) syndromes, including Ohdo syndrome of the Maat...

Case of Smith-Magenis Syndrome.

Traumatic globe rupture in a patient with Marshall-Smith Syndrome.

Medical and Biotech [MESH] Definitions

An autosomal recessive disorder of CHOLESTEROL metabolism. It is caused by a deficiency of 7-dehydrocholesterol reductase, the enzyme that converts 7-dehydrocholesterol to cholesterol, leading to an abnormally low plasma cholesterol. This syndrome is characterized by multiple CONGENITAL ABNORMALITIES, growth deficiency, and MENTAL RETARDATION.

Complex neurobehavioral disorder characterized by distinctive facial features (FACIES), developmental delay and mental retardation. Behavioral phenotypes include sleep disturbance, maladaptive, self-injurious and attention-seeking behaviors. The sleep disturbance is linked to an abnormal circadian secretion pattern of MELATONIN. The syndrome is associated with de novo deletion or mutation and HAPLOINSUFFICIENCY of the retinoic acid-induced 1 protein on chromosome 17p11.2.

Condition with a variable constellation of phenotypes due to deletion polymorphisms at chromosome location 22q11. It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. In addition, variable developmental problems and schizoid features are also associated with this syndrome. (From BMC Med Genet. 2009 Feb 25;10:16) Not all deletions at 22q11 result in the 22q11deletion syndrome.

Rare congenital disorder with multiple anomalies including: characteristic dysmorphic craniofacial features, musculoskeletal abnormalities, neurocognitive delay, and high prevalence of cancer. Germline mutations in H-Ras protein can cause Costello syndrome. Costello syndrome shows early phenotypic overlap with other disorders that involve MAP KINASE SIGNALING SYSTEM (e.g., NOONAN SYNDROME and cardiofaciocutaneous syndrome).

An autosomal dominant aneurysm with multisystem abnormalities caused by increased TGF-BETA signaling due to mutations in type I or II of TGF-BETA RECEPTOR. Additional craniofacial features include CLEFT PALATE; CRANIOSYNOSTOSIS; HYPERTELORISM; or bifid uvula. Phenotypes closely resemble MARFAN SYNDROME; Marfanoid craniosynostosis syndrome (Shprintzen-Goldberg syndrome); and EHLERS-DANLOS SYNDROME.

More From BioPortfolio on "Estimation of the Carrier Frequency and Incidence of Smith-Lemli-Opitz Syndrome in African Americans"

Quick Search

Relevant Topics

Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Searches Linking to this Trial