Localization of a translocation breakpoint involved in Smith-Lemli-Opitz syndrome

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134378

Alley, T L; Gray, B A; Lee, S ^[1]

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1. 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--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOSYNTHESIS
CHOLESTEROL
CHROMOSOMAL ABERRATIONS
CONGENITAL MALFORMATIONS
DNA HYBRIDIZATION
DNA-CLONING
FLUORESCENCE
GENE MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 7
HUMAN CHROMOSOMES
MENTAL DISORDERS
METABOLISM
PATIENTS
PHENOTYPE
RECESSIVE MUTATIONS
YEASTS