Jansen-type metaphyseal chondrodysplasia: analysis of PTH/PTH-related protein receptor messenger RNA by the reverse transcriptase-polymerase chain method.
Jansen-type metaphyseal chondrodysplasia: analysis of PTH/PTH-related protein receptor messenger RNA by the reverse transcriptase-polymerase chain method.
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Jansen型干骺端软骨发育不良：逆转录酶-聚合酶链法分析PTH/PTH相关蛋白受体信使RNA。
DOI：
10.1507/endocrj.44.493
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发表时间：
1997
影响因子：
2
通讯作者：
Hiroo Niimi
中科院分区：
文献类型：
--
作者：
M. Minagawa;Kazuo Arakawa;S. Takeuchi;K. Minamitani;T. Yasuda;Hiroo Niimi
jansen型干骺端软骨发育不良（JMC）具有长骨骨化延迟和高钙血症。我们报告了一位日本男性JMC患者，他在3个月大（mo）时表现为佝偻病症状，高钙血症（13 mg/dl）和低%TRP。高钙血症的治疗时间为3个月至11岁。在13岁时，x线片上发现骨形逐渐变宽、展裂和碎裂，导致管状骨变短，身高也随之变矮[107厘米（-6.5标准差）]。高钙血症趋于正常化，13% TRP恢复正常。反复测量血清甲状旁腺激素和甲状旁腺激素相关蛋白（PTHrP）水平显示，在高钙血症和高尿cAMP排泄时，它们处于低或正常水平。这让我们怀疑PTH/PTHrP受体的组成性激活。对来自皮肤成纤维细胞的PTH/PTHrP受体互补DNA的直接测序显示，在该受体第二跨膜区域的90%的DNA片段中，CAC向CGC的转化产生了严格保守的His223向Arg的取代。该突变产生了一个限制性位点Sphl （G/CATG/C）。基因组DNA的直接测序和限制性内切酶酶切显示了杂合转变。在表型正常的亲本中不存在该突变。我们得出结论，在JMC中，发育不良的骨病变和钙稳态都是年龄依赖性的，并且无论种族差异如何，在4名表型相似的高加索患者中发现的His223-Arg替换是相同的，并且尽管基因组DNA发生异卵性逆转，但皮肤成纤维细胞中PTH/PTHrP受体mRNA异常等位基因的优先表达表明等位基因表达的重要性。
Jansen-type metaphyseal chondrodysplasia (JMC) has both delayed ossification in long bones and usually hypercalcemia. We report a Japanese male patient with JMC who presented with rachitic signs on radiographs, hypercalcemia (13 mg/dl) and low %TRP at age 3 months (mo). Hypercalcemia was treated from age 3 mo to 11 yr. Progressive widening, splaying and fragmentation of the metaphyses have been recognized on radiographs which resulted in shortened tubular bones and consequent short stature [107 cm (-6.5 SD)] at age 13 yr. Hypercalcemia tended to normalize, and %TRP became normal at age 13 yr. Repeated measurements of serum PTH and PTH-related protein (PTHrP) levels showed that they were low or normal in the face of hypercalcemia and high urine cAMP excretion, which led us to suspect constitutive activation of the PTH/PTHrP receptor. Direct sequencing of PTH/PTHrP receptor complementary DNA from skin fibroblast cells revealed a CAC to CGC transversion yielding a strictly conserved His223 to Arg substitution found in 90% of DNA fragment in the second transmembrane domain of the receptor. This mutation created a restriction site Sphl (G/CATG/C). Direct sequencing of genomic DNA and also restriction enzyme digestion revealed heterozygous transition. The mutation was absent in the parents with normal phenotype. We conclude that both dysplastic bone lesions and calcium homeostasis are age-dependent in JMC, and that the His223-Arg substitution is the same as that found in four Caucasian patients with a similar phenotype irrespective of the ethnic difference, and that the preferential expression of an abnormal allele of the PTH/PTHrP receptor mRNA in skin fibroblast despite heterogygotic transversion in the genomic DNA suggests the importance of allele expression.
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影响因子：
10.5
作者：
KARAPLIS, AC;LUZ, A;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
影响因子：
56.9
作者：
JUPPNER, H;ABOUSAMRA, AB;SEGRE, GV
通讯作者：
SEGRE, GV
影响因子：
56.9
作者：
LIN, HY;HARRIS, TL;GOLDRING, SR
通讯作者：
GOLDRING, SR
相同的互补脱氧核糖核酸编码人肾和骨甲状旁腺激素 (PTH)/PTH 相关肽受体。
影响因子：
4.8
作者：
Schipani,E;Karga,H;Karaplis,AC;PottsJr,JT;Kronenberg,HM;Segre,GV;Abou-Samra,AB;Juppner,H
通讯作者：
Juppner,H