A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene
A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene
复制标题
DOI：
10.1016/j.bone.2011.06.029
复制
发表时间：
2011-10-01
期刊：
影响因子：
4.1
通讯作者：
Fujitab, Toshiro
中科院分区：
文献类型：
--
作者：
Saito, Tasuku;Shimizu, Yuichiro;Fujitab, Toshiro
X连锁低磷血症性佝偻病/骨软化症（XLH）、常染色体显性低磷血症性佝偻病/骨软化症（ADHR）和常染色体隐性低磷血症性佝偻病/骨软化症（ARHR 1或ARHR 2）是遗传性成纤维细胞生长因子23（FGF 23）相关的低磷血症性佝偻病，具有相似的临床特征。我们在这里展示一个病人低血磷性佝偻病和广泛骨化的后纵韧带（OPLL）。先证者是一名62岁的女性。她的父母是堂兄弟姐妹，没有佝偻病或骨软化症的迹象。她表现出低磷酸盐血症性佝偻病伴FGF 23水平升高，临床上被认为患有XLH。然而，直接测序与X染色体上的内肽酶（PHEX），FGF 23和牙本质基质蛋白1（DMPI）基因（分别负责XLH，ADHR和ARHR 1的基因）同源的磷酸盐调节基因的所有编码外显子和外显子-内含子连接未显示突变。在ARHR 2的外核苷酸焦磷酸酶/磷酸二酯酶1（ENPP 1）基因外显子21的外显子-内含子连接处发现一个新的纯合剪接供体位点突变（IVS 21 + 1_3（GTA>CACC））。随后的mRNA分析显示，该突变导致外显子21跳跃，从而在外显子22中产生提前终止密码子。这些结果表明，遗传分析是强制性的正确诊断遗传性FGF 23相关的低磷酸盐血症佝偻病。由于Enpp 1基因敲除小鼠是OPLL的模型，该病例也表明OPLL与ARHR 2相关。(C)2011 Elsevier Inc. All rights reserved.
X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and autosomal recessive hypophosphatemic rickets/osteomalacia (ARHR1 or ARHR2) are hereditary fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets showing similar clinical features. We here show a patient with hypophosphatemic rickets and widespread ossification of posterior longitudinal ligament (OPLL). The proband is a 62-year-old female. Her parents are first cousins and showed no signs of rickets or osteomalacia. She showed hypophosphatemic rickets with elevated FGF23 level and had been clinically considered to be suffering from XLH. However, direct sequencing of all coding exons and exon-intron junctions of phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX), FGF23 and dentin matrix protein 1 (DMPI) genes, responsible genes for XLH, ADHR and ARHR1, respectively, showed no mutation. A novel homozygous splice donor site mutation was found at the exon-intron junction of exon 21 of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene responsible for ARHR2 (IVS21 + 1_3 (GTA>CACC)). Subsequent analysis of mRNA revealed that this mutation caused skipping of exon 21 which created a premature stop codon in exon 22. These results indicate that genetic analysis is mandatory for the correct diagnosis of hereditary FGF23-related hypophosphatemic rickets. Because Enpp1 knockout mouse is a model of OPLL, this case also suggests that OPLL is associated with ARHR2. (C) 2011 Elsevier Inc. All rights reserved.