Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene.
Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene.
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DOI：
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发表时间：
1991-11
影响因子：
9.8
通讯作者：
P. Venta;R. J. Welty;T. M. Johnson;W. Sly;R. Tashian
中科院分区：
文献类型：
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作者：
P. Venta;R. J. Welty;T. M. Johnson;W. Sly;R. Tashian
碳酸酐酶II（CA II），它具有最高的营业额和最广泛的组织分布的任何已知的七种CA同工酶在人类，是缺乏的红细胞和可能从其他组织的CA II缺乏综合征的患者。我们对一个比利时家庭近亲结婚的患者的CA II基因进行了测序，并确定了可能导致该家庭CA II缺乏症的突变。该变化是C到T的转变，其导致在位置107处Tyr（达特）取代His（CAT）。组氨酸是不变的，在所有羊膜CA同工酶测序的日期，以及CA从板鳃类和藻类来源，并在病毒CA相关蛋白。His-107似乎在所有CA分子的结构中具有稳定功能，并且其被Tyr取代显然破坏了His-107与另外两个类似不变残基Glu-117和Tyr-194的关键氢键，导致不稳定的CA II分子。我们还完成了正常人CA II基因的内含子-外显子结构，这使我们能够为所有外显子制备PCR引物。这些引物将有助于确定其他遗传性CA II缺陷中的突变。
Carbonic anhydrase II (CA II), which has the highest turnover number and widest tissue distribution of any of the seven CA isozymes known in humans, is absent from the red blood cells and probably from other tissues of patients with CA II deficiency syndrome. We have sequenced the CA II gene in a patient from a consanguinous marriage in a Belgian family and identified the mutation that is probably the cause of the CA II deficiency in that family. The change is a C-to-T transition which results in the substitution of Tyr (TAT) for His (CAT) at position 107. This histidine is invariant in all amniotic CA isozymes sequenced to date, as well as the CAs from elasmobranch and algal sources and in a viral CA-related protein. His-107 appears to have a stabilizing function in the structure of all CA molecules, and its substitution by Tyr apparently disrupts the critical hydrogen bonding of His-107 to two other similarly invariant residues, Glu-117 and Tyr-194, resulting in an unstable CA II molecule. We have also completed the intron-exon structure of the normal human CA II gene, which has allowed us to prepare PCR primers for all exons. These primers will facilitate the determination of the mutations in other inherited CA II deficiencies.