The Langer-Giedion syndrome: Molecular dissection of a contiguous gene syndrome

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

OSTI ID:134441

Luedecke, H J; Pillo, B L; Nardmann, J ^[1]

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1. Universitaetsklinikum Essen (Germany); and others

The tricho-rhino-phalangeal syndromes TRPS I and II, which are characterized by craniofacial dysmorphism and skeletal abnormalities, are caused by genetic defects in 8q24.1. The presence of multiple exostoses (EXT) distinguishes TRPS II (Langer-Giedion syndrome, LGS) from TRPS I. Multiple exostoses also occur as an autosomal dominant trait displaying genetic heterogeneity. One of the EXT loci maps to 8q24.1. Previously, we had determined a probe order (cen-D8S50-D8S98-D8S51-D8S67-D8S43-tel) for the Langer-Giedion syndrome chromosome region. The shortest region of deletion overlap in LGS patients is defined by D8S51 and D8S67. Interestingly, a patient with TRPS I and a large deletion was found to be intact for these two loci, but deleted for more proximal loci. We have now constructed a complete yeast artificial chromosome (YAC) contig for the entire LGCR. Some of these YACs were used to perform fluorescence in situ hybridization analyses in patients with chromosomal abnormalities associated with TRPS I, TRPS II and EXT. One YAC containing D8S98 spans the translocation breakpoint in a patient with TRPS I and (8;18)(q24.11;q13.3;q21.13). The translocation breakpoint in a patient with TRPS II and t(4;8)(p15.3;q24.1) is covered by a D8S67 YAC. Interestingly, this YAC also spans the inversion breakpoint in a patient with EXT and inv(8)(p23;q24.1). The data indicate that most of the putative TRPS I gene is located between D8S98 and D8S51, that the putative EXT gene maps to D8S67, and that both genes are 1.5 Mbp apart. We are currently analyzing putative gene sequences in the vicinity of the chromosomal breakpoints.

• OSTI ID: 134441
• 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
BIOLOGICAL MARKERS
CHROMOSOMAL ABERRATIONS
CONGENITAL MALFORMATIONS
CONTIGS
DNA HYBRIDIZATION
DNA SEQUENCING
DOMINANT MUTATIONS
FLUORESCENCE
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 18
HUMAN CHROMOSOME 8
PATIENTS
PROBES
SIZE
SKELETAL DISEASES
YEASTS