X-linked hypoparathyroidism region on Xq27 is evolutionarily conserved with regions on 3q26 and 13q34 and contains a novel P-type ATPase.
X-linked hypoparathyroidism region on Xq27 is evolutionarily conserved with regions on 3q26 and 13q34 and contains a novel P-type ATPase.
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Xq27 上的 X 连锁甲状旁腺功能减退症区域在进化上与 3q26 和 13q34 上的区域一样保守，并且包含一种新型 P 型 ATP 酶。
DOI：
10.1016/j.ygeno.2004.08.003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Thakker,RajeshV
中科院分区：
文献类型：
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作者：
AndrewNesbit,M;Bowl,MichaelR;Harding,Brian;Schlessinger,David;Whyte,MichaelP;Thakker,RajeshV
x连锁甲状旁腺功能低下（HPT）已被定位到染色体Xq27上一个988-kb的区域，该区域包含三个基因，MCF2/DBL， SOX3和U7snRNA同源基因，以及部分cDNA AS6。我们分离了全长AS6 cDNA，确定了其基因组组织，并在HPT患者中寻找异常。AS6被鉴定为ATP11C的3 ' UTR， ATP11C是p型ATPases的一个新成员，由31个具有替代转录本的外显子组成。ATP11C与SOX3和MCF2/DBL在Xq27上的共定位与ATP11A与SOX1和MCF2L在13q34和ATP11B与SOX2在3q26上的共定位相同。这些共定位在小鼠中是进化保守的，分析表明SOX2的分化可能发生在SOX1和SOX3分离之前。HPT患者的ATP11C、MCF2、SOX3和U7snRNA分析未发现突变，这意味着在x连锁甲状旁腺功能低下的病因学中，一种尚未确定的基因发生了调控变化或突变。
X-linked hypoparathyroidism (HPT) has been mapped to a 988-kb region on chromosome Xq27 that contains three genes, MCF2/DBL, SOX3, and U7snRNA homologue, and a partial cDNA, AS6. We isolated the full-length AS6 cDNA, determined its genomic organization, and sought for abnormalities in HPT patients. AS6 was identified as the 3′ UTR of ATP11C, a novel member of the P-type ATPases, which consists of 31 exons with alternative transcripts. The colocalization of ATP11C with SOX3 and MCF2/DBL on Xq27 mirrors that of ATP11A with SOX1 and MCF2L on 13q34 and ATP11B with SOX2 on 3q26. These colocalizations are evolutionarily conserved in mouse, and analyses indicate that SOX2 divergence likely occurred before the separation of SOX1 and SOX3. Analyses of ATP11C, MCF2, SOX3, and U7snRNA in HPT patients did not reveal mutations, implicating regulatory changes or mutation of an as yet unidentified gene in the etiology of X-linked hypoparathyroidism.