Details

Autor(en) / Beteiligte

• Roth, Donna E.
• Venta, Patrick J.
• Tashian, Richard E.
• Sly, William S.

Titel

Molecular Basis of Human Carbonic Anhydrase II Deficiency

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1992-03, Vol.89 (5), p.1804-1808

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1992

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.