Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification.

Proceedings of the National Academy of Sciences of the United States of America - Tập 80 Số 9 - Trang 2752-2756 - 1983
William S. Sly1,2,3, David Hewett‐Emmett, Michael P. Whyte, Yahong Yu, Richard E. Tashian
1Departments of Pediatrics, Medicine, and Genetics, Washington University School of Medicine, Division of Medical Genetics, St. Louis Children's Hospital, St. Louis, Missouri 63110; tDivision of Bone and Metabolism, Departments of Medicine and Pediatrics,
2University of Michigan Medical School, Ann Arbor, Michigan 48109
3Washington University School of Medicine and the Jewish Hospital of St. Louis, St. Louis, Missouri 63110; and tDepartment of Human Genetics,

Tóm tắt

The clinical, radiological, and pathological findings in three siblings affected with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification have been reported. In an effort to explain the pleiotropic effects of the mutation producing this disorder, we postulated a defect in carbonic anhydrase II (CA II), the only one of the three soluble isozymes of carbonic anhydrase that is known to be synthesized in kidney and brain. We report here biochemical and immunological evidence for the virtual absence of CA II in erythrocytes of patients affected with this condition, whereas CA I level is not reduced. Levels of CA II in erythrocyte hemolysates from asymptomatic obligate heterozygotes are about half of normal. These findings: (i) elucidate the basic defect in one form of inherited osteopetrosis; (ii) provide genetic evidence implicating CA II in osteoclast function and bone resorption; (iii) explain previous observations that carbonic anhydrase inhibitors block the normal parathyroid hormone-induced release of calcium from bone; (iv) clarify the role of renal CA II in urinary acidification and bicarbonate reabsorption; and (v) suggest a method to identify heterozygous carriers for the gene for this recessively inherited syndrome.

Từ khóa


Tài liệu tham khảo

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 80 Số 9

2752-2756

Thông tin tác giả