CARBONIC ANHYDRASE-II DEFICIENCY IDENTIFIED AS THE PRIMARY DEFECT IN THE AUTOSOMAL RECESSIVE SYNDROME OF OSTEOPETROSIS WITH RENAL TUBULAR-ACIDOSIS AND CEREBRAL CALCIFICATION
CARBONIC ANHYDRASE-II DEFICIENCY IDENTIFIED AS THE PRIMARY DEFECT IN THE AUTOSOMAL RECESSIVE SYNDROME OF OSTEOPETROSIS WITH RENAL TUBULAR-ACIDOSIS AND CEREBRAL CALCIFICATION
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DOI：
10.1073/pnas.80.9.2752
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
TASHIAN, RE
中科院分区：
文献类型：
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作者：
SLY, WS;HEWETTEMMETT, D;TASHIAN, RE
报道了 3 名患有常染色体隐性遗传骨硬化综合征并伴有肾小管酸中毒和脑钙化的兄弟姐妹的临床、放射学和病理学结果。为了解释产生这种疾病的突变的多效性，假设碳酸酐酶 II (CA II) 存在缺陷，这是已知在肾脏和大脑中合成的碳酸酐酶 3 种可溶性同工酶中唯一的一种。据报道，生化和免疫学证据表明，患有这种疾病的患者的红细胞中几乎不存在 CA II，而 CA I 水平并未降低。无症状专性杂合子的红细胞溶血液中 CA II 水平约为正常值的一半。这些发现： 阐明了一种遗传性石骨症的基本缺陷；提供表明 CA II 与破骨细胞功能和骨吸收有关的遗传证据；解释之前的观察结果，即碳酸酐酶抑制剂会阻止正常甲状旁腺激素诱导的骨钙释放；阐明肾 Ca II 在尿液酸化和碳酸氢盐重吸收中的作用；并提出了一种识别这种隐性遗传综合征基因杂合携带者的方法。
The clinical, radiological and pathological findings in 3 siblings affected with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification were reported. In an effort to explain the pleiotropic effects of the mutation producing this disorder, a defect was postulated in carbonic anhydrase II (CA II), the only one of the 3 soluble isozymes of carbonic anhydrase that is known to be synthesized in kidney and brain. Biochemical and immunological evidence is reported 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: elucidate the basic defect in one form of inherited osteopetrosis; provide genetic evidence implicating CA II in osteoclast function and bone resorption; explain previous observations that carbonic anhydrase inhibitors block the normal parathyroid hormone-induced release of calcium from bone; clarify the role of renal Ca II in urinary acidification and bicarbonate reabsorption; and suggest a method to identify heterozygous carriers for the gene for this recessively inherited syndrome.