DENTS DISEASE, A RENAL FANCONI SYNDROME WITH NEPHROCALCINOSIS AND KIDNEY-STONES, IS ASSOCIATED WITH A MICRODELETION INVOLVING DXS255 AND MAPS TO XP11.22
DENTS DISEASE, A RENAL FANCONI SYNDROME WITH NEPHROCALCINOSIS AND KIDNEY-STONES, IS ASSOCIATED WITH A MICRODELETION INVOLVING DXS255 AND MAPS TO XP11.22
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DOI：
10.1093/hmg/2.12.2129
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发表时间：
1993-12-01
影响因子：
3.5
通讯作者：
THAKKER, RV
中科院分区：
文献类型：
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作者：
POOK, MA;WRONG, O;THAKKER, RV
登特氏病是一种家族性近端肾小管疾病，其与低分子量蛋白尿、高钙尿、肾钙质沉着、肾结石和肾衰竭相关。这种疾病的遗传方式和主要缺陷尚不清楚。对5个不相关的英国家庭的分析显示，男性的疾病严重程度更高，并且没有男性到男性的传播。这表明一个X连锁遗传，我们进一步调查了33名成员（12名受影响，21名未受影响）从两个3代家庭的连锁研究。利用20个X连锁多态性标记与Xp 11基因座ARAF 1、DXS 426、DXS 255和DXS 988建立了连锁关系，最高LOD值和重组分数（θ）分别为5.42（θ = 0.000）、3.61（θ = 0.000）、5.48（θ = 0.000）和4.25（θ = 0.045）。此外，DXS 255在一个家族的受影响成员中发现了微缺失，从而进一步将Dent病定位于Xp11.22。组合的多基因座连锁分析和缺失作图研究定义了基因座顺序Xpter-MAOB-（ARAF 1，DXS 426）-SYP-TFE 3-（DXS 255，DENT’S）-DXS 988-Xcen，从而将与Dent’s病相关的微缺失作图至侧翼为TFE 3和DXS 988的4厘摩间隔。因此，登特氏病是一种X连锁疾病，与Xp11.22的微缺失有关，进一步表征该基因将有助于阐明控制近端肾小管功能和肾结石发展的因素。
Dent's disease is a familial proximal renal tubular disorder which is associated with low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, kidney stones and renal failure. The mode of inheritance and the primary defect for this disorder are unknown. An analysis of 5 unrelated British families revealed a greater disease severity in males and an absence of male to male transmission. This suggested an X-linked inheritance and we investigated this further by linkage studies in 33 members (12 affected, 21 unaffected) from two 3-generation families. Twenty X-linked polymorphic markers were used and linkage was established with the Xp11 loci ARAFl, DXS426, DXS255 and DXS988 with peak LOD scores and recombination fractions (theta) of 5.42 (theta = 0.000), 3.61 (theta = 0.000), 5.48 (theta = 0.000) and 4.25 (theta = 0.045) respectively. In addition, DXS255 revealed a microdeletion in the affected members of one family, thereby further localising Dent's disease to Xp11.22. Combined multilocus linkage analysis and deletion mapping studies defined the locus order Xpter-MAOB-(ARAFl, DXS426)-SYP-TFE3-(DXS255, DENT'S)-DXS988-Xcen, thereby mapping the microdeletion associated with Dent's disease to a 4 centiMorgan interval flanked by TFE3 and DXS988. Thus, Dent's disease is an X-linked disorder which is associated with a microdeletion of Xp11.22, and a further characterisation of this gene will help to elucidate the factors controlling proximal renal tubular function and the development of kidney stones.