Mutations in DDR2 Gene Cause SMED with Short Limbs and Abnormal Calcifications
Mutations in DDR2 Gene Cause SMED with Short Limbs and Abnormal Calcifications
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DOI：
10.1016/j.ajhg.2008.12.004
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发表时间：
2009-01-09
影响因子：
9.8
通讯作者：
Raas-Rothschild, Annick
中科院分区：
文献类型：
--
作者：
Bargal, Ruth;Cormier-Daire, Valerie;Raas-Rothschild, Annick
脊柱-间-骨骺发育不良[SMED]短肢-手型[SMED-SL]是一种罕见的常染色体隐性遗传病，由Borochowitz等于1993年首次报道。(1)自那时以来，已报告了14名受影响的患者。(2-5)我们诊断了6例来自耶路撒冷地区5个不同血缘的阿拉伯穆斯林家庭的SMED-SL患者。此外，我们还研究了两名阿尔及利亚和巴基斯坦血统的患者以及第一批犹太患者的父母。(1)使用纯合性作图策略，我们位于染色体1 q23跨越2.4 Mb的候选区域。盘状结构域受体2（DDR2）基因在候选区域内的位置以及DDR2敲除小鼠与SMED患者表型的相似性促使我们研究该基因（6）。我们鉴定了三个错义突变c.2254C> T [R752 C]，c. 2177 T > G [1726 R]，c.2138C > T [T7131]和编码DDR2基因酪氨酸激酶结构域的保守序列中的一个剪接位点突变[IVS 17 +1g > a]。这项研究的结果将允许一个准确的早期产前诊断和携带者筛查的风险家庭。
The spondylo-meta-epiphyseal dysplasia [SMED] short limb-hand type [SMED-SL] is a rare autosomal-recessive disease, first reported by Borochowitz et al. in 1993.(1) Since then, 14 affected patients have been reported.(2-5) We diagnosed 6 patients from 5 different consanguineous Arab Muslim families from the Jerusalem area with SMED-SL. Additionally, we studied two patients from Algerian and Pakistani ancestry and the parents of the first Jewish patients reported.(1) Using a homozygosity mapping strategy, we located a candidate region on chromosome 1q23 spanning 2.4 Mb. The position of the Discoidin Domain Receptor 2 (DDR2) gene within the candidate region and the similarity of the ddr2 knockout mouse to the SMED patients' phenotype prompted us to study this gene(6). We identified three missense mutations c.2254 C > T [R752C], c. 2177 T > G [1726R], c.2138C > T [T7131] and one splice site mutation [IVS17+1g > a] in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene. The results of this study will permit an accurate early prenatal diagnosis and carrier screening for families at risk.