Mutations at the lysosomal acid cholesteryl ester hydrolase gene locus in Wolman disease

Journal Article · Tue Mar 29 04:00:00 EST 1994 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.91.7.2718· OSTI ID:86526

Anderson, R A; Byrum, R S ^[1]; Coates, P M ^[2]; Sando, G N ^[3]

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1. Wake Forest Univ. Medical Center, Winston-Salem, NC (United States)
2. Children`s Hospital of Philadelphia, PA (United States)
3. Univ. of Iowa, Iowa City, IA (United States)

The genomic sequences encoding the human lysosomal acid lipase/cholesteryl esterase (sterol esterase; EC 3.1.1.13) have been isolated and sequenced, and the information has been used to identify mutations in both alleles of the gene from a patient with Wolman disease, an autosomal recessive lysosomal lipid storage disorder. The genomic locus consists of 10 exons spread over 36 kb. The 5{prime} flanking region is G+C-rich and has characteristics of a {open_quotes}housekeeping{close_quotes} gene promoter. One of the identified mutations involves the insertion of a T residue after position 634, resulting in the appearance of an in-frame translation stop signal 13 codons downstream. The second mutation is a T-to-C transition at nucleotide 638. This results in a leucine-to-proline substitution at amino acid 179 and is predicted to lead to the disruption of the {alpha}-helical structure in a highly conserved region of the protein. These mutations are each capable of completely disrupting the catalytic function of the lysosomal acid cholesteryl phenotype of the lysosomal lipid storage disorder mainifested in members of this patient`s family. 26 refs., 6 figs.

• Sponsoring Organization: USDOE
• OSTI ID: 86526
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 7 Vol. 91; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CARBOXYLESTERASES
CHOLESTEROL
GENE MUTATIONS
LIPIDS
LYSOSOMES
METABOLIC DISEASES