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.
These will be newborn screening blood spots from African American babies. Samples from
Blacks of African, Caribbean and Central American descent will be included. The
classification of the infants will be based on the maternal identification as Black or
African American by blood spot submission card.
Newborn screening blood spots from non-African American or non-Black babies.