Localization of a translocation breakpoint involved in Smith-Lemli-Opitz syndrome
- Univ. of Florida, Gainesville, FL (United States); and others
Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomaly/mental retardation syndrome, with features including toe syndactyly, genital anomalies, unusual facies, and occasional organ malformations. The gene(s) for this autosomal recessive disorder has not been mapped. Recent biochemical studies suggest that the defect may involve the penultimate step in cholesterol synthesis, as patients have low serum cholesterol and increased 7-dehydrocholesterol (7-DHC) levels. However, the enzyme putatively involved (7-DHC reductase) has not been isolated. We identified an SLOS patient with a de novo balanced chromosome translocation [t(7;20)(q32.1;q13.2)], and we propose that the translocation interrupts one of the patient`s SLOS alleles. We are pursuing positional cloning to identify the SLOS gene. Using fluorescence in situ hybridization (FISH), we recently identified a chromosome 7 yeast artificial chromosome (YAC) that spans the breakpoint and places it onto physical and genetic maps. We are in the process of narrowing this region via overlapping YACs and YAC subclones, from which we will isolate candidate cDNAs. Any candidate gene disrupted by the translocation and mutated on the other allele will be proven to be the SLOS gene. Functional analysis of an SLOS cDNA may also determine its relationship to cholesterol metabolism and the observed biochemical abnormalities.
- OSTI ID:
- 134378
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1112
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Smith-Lemli-Opitz syndrome in a female with a de novo, balanced translocation involving 7q32: Probable disruption of an SLOS gene
Physical mapping of the chromosome 7 breakpoint region in an SLOS patient with t(7;20)X(q32.1;q13.2)
Related Subjects
BASIC STUDIES
PATIENTS
PHENOTYPE
HEREDITARY DISEASES
CONGENITAL MALFORMATIONS
MENTAL DISORDERS
GENES
GENE MUTATIONS
GENETIC MAPPING
HUMAN CHROMOSOMES
CHROMOSOMAL ABERRATIONS
CHOLESTEROL
BIOSYNTHESIS
METABOLISM
HUMAN CHROMOSOME 7
RECESSIVE MUTATIONS
DNA-CLONING
DNA HYBRIDIZATION
FLUORESCENCE
YEASTS