Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1804-8.

Molecular basis of human carbonic anhydrase II deficiency.

Author information

  • 1Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, MO 63104.

Abstract

Deficiency of carbonic anhydrase II (carbonate hydro-lyase, EC 4.2.1.1) is the primary defect in the syndrome of osteopetrosis, renal tubular acidosis, and cerebral calcification. In this report we describe the molecular basis for carbonic anhydrase II deficiency in the American family in which the association of carbonic anhydrase II deficiency with this syndrome was first recognized. The three affected siblings from this family are compound heterozygotes, each having inherited two different mutations in the structural gene for carbonic anhydrase II. The paternal mutation is a splice acceptor site mutation at the 3' end of intron 5. The maternal mutation is a missense mutation in exon 3 that substitutes a tyrosine for histidine-107. We show that the mutant enzyme expressed in bacteria from the cDNA containing the His-107----Tyr mutation has detectable, though greatly reduced, activity. We suggest that residual activity of the His-107----Tyr mutant enzyme may explain the absence of mental retardation and the relatively mild phenotype of carbonic anhydrase II deficiency in affected members of this family.

PMID:
1542674
[PubMed - indexed for MEDLINE]
PMCID:
PMC48541
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk