位于Xq27的X连锁低甲状旁腺功能减退症区域在进化上与位于3q26和13q34的区域保守，并包含一种新型P型ATP酶。

X-linked hypoparathyroidism region on Xq27 is evolutionarily conserved with regions on 3q26 and 13q34 and contains a novel P-type ATPase.

作者信息

Andrew Nesbit M, Bowl Michael R, Harding Brian, Schlessinger David, Whyte Michael P, Thakker Rajesh V

机构信息

Academic Endocrine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, UK.

出版信息

Genomics. 2004 Dec;84(6):1060-70. doi: 10.1016/j.ygeno.2004.08.003.

DOI:10.1016/j.ygeno.2004.08.003

PMID:15533723

Abstract

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.

摘要

X连锁低甲状旁腺功能减退症（HPT）已被定位到Xq27上一个988kb的区域，该区域包含三个基因，即MCF2/DBL、SOX3和U7snRNA同源物，以及一个部分cDNA，AS6。我们分离出了全长AS6 cDNA，确定了其基因组结构，并在HPT患者中寻找异常情况。AS6被鉴定为ATP11C的3'非翻译区，ATP11C是P型ATP酶的一个新成员，由31个外显子和可变转录本组成。ATP11C与SOX3和MCF2/DBL在Xq27上的共定位与ATP11A与SOX1和MCF2L在13q34上以及ATP11B与SOX2在3q26上的共定位相似。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。对HPT患者的ATP11C、MCF2、SOX3和U7snRNA的分析未发现突变，这表明X连锁低甲状旁腺功能减退症的病因可能涉及调控变化或一个尚未确定的基因的突变。