Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA

Journal Article · Wed Mar 01 04:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.6.1919· OSTI ID:7018773

Gibbs, R A ^[1]; Nguyen, Phinga ^[2]; McBride, L J; Koepf, S M ^[3]; Caskey, C T ^[4]

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1. Baylor College of Medicine, Houston, TX (USA)
2. Howard Hughes Medical Institute, Houston, TX (USA)
3. Applied Biosystems, Foster City, CA (USA)
4. Baylor College of Medicine, Houston, TX (USA) Howard Hughes Medical Institute, Houston, TX (USA)

The Lesch-Nyhan (LN) syndrome is a severe X chromosome-linked disease that results from a deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT). The mutations leading to the disease are heterogeneous and frequently arise as de novo events. The authors have identified nucleotide alterations in 15 independently arising HPRT-deficiency cases by direct DNA sequencing of in vitro amplified HPRT cDNA. They also demonstrate that the direct DNA sequence analysis can be automated, further simplifying the detection of new mutations at this locus. The mutations include DNA base substitutions, small DNA deletions, a single DNA base insertion, and errors in RNA splicing. The application of these procedures allows DNA diagnosis and carrier identification by the direct detection of the mutant alleles within individual families affected by LN.

• OSTI ID: 7018773
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:6; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550401* -- Genetics-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
AUTOMATION
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHROMOSOMES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DISEASES
DNA
DNA SEQUENCING
ENZYMES
GENE AMPLIFICATION
GENE MUTATIONS
GLYCOSYL TRANSFERASES
HEREDITARY DISEASES
HETEROCHROMOSOMES
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
IN VITRO
ISOTOPES
LEUKOCYTES
LIGHT NUCLEI
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MUTATIONS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PENTOSYL TRANSFERASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RECOMBINANT DNA
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
VERTEBRATES
X CHROMOSOME