婴儿型低磷酸酶血症组织非特异性碱性磷酸酶基因突变检测

Infantile hypophosphatasia due to mutations in the tissue-nonspecific alkaline phosphatase gene

目的 对1例婴儿型低磷酸酶血症患者及其父母进行临床分析和基因突变检测,以探讨该病的致病机制.方法 针对1例罕见的婴儿型低磷酸酶血症患者进行实验室检验及影像学检查.进而提取患儿及其亲属外周血基因组DNA,采用针对组织非特异性碱性磷酸酶ALPL基因调控区及编码区的特异性引物进行PCR扩增,直接对产物进行测序,并对所鉴定的突变在无关人群中进行验证.结果 患儿血碱性磷酸酶水平显著降低,同时存在高钙血症、中度贫血及双肾钙化；骨骼具有佝偻病样改变.ALPL基因测序结果显示患儿为复合杂合突变,同时携带位于第7外显子的c.814C ＞T （p.R272C）错义突变及位于第9外显子的c.1101_1103 delCTC （p.S368 del）碱基缺失突变.临床表现正常的患儿母亲、父亲为杂合子,分别携带c.1101_1103 delCTC （p.S368del）碱基缺失突变及c.814C ＞T （p.R272C）错义突变.该家系符合常染色体隐性遗传,50例无关健康个体验证未发现上述两种突变存在.结论 ALPL基因c.814C＞T（p.R272C）和c.1101_1103 delCTC（p.S368del）突变与该家系婴儿型低磷酸酶血症临床表现密切相关.

Objective To explore the clinical and genetic characteristics of a Chinese boy with infantile hypophosphatasia. Methods The clinical data of the boy was carefully collected. The laboratory and radiographic examination were taken in the case. Sequencing for all the twelve ALPL exons and the flanking exon-intron junctions was performed in the proband and his parents with their genomic DNA. Results Two mutations were found with one missense mutation c. 814C 〉 T （p. R272C） in the proband and his father and the other deletion mutation c. 1101_1103 delCTC （p. $368del） in the propand and his mother. The propand was manifested as a compound heterozygotes of the two mutations. The mutations were not detected in fifty normal controls. Conclusion The result suggests that the compound heterozygous mutation in ALPL is responsible for infantile hypophosphatasia in the Chinese family.