CAJ | 학술논문

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.
목적 대1례영인형저린산매혈증환자급기부모진행림상분석화기인돌변검측,이탐토해병적치병궤제.방법 침대1례한견적영인형저린산매혈증환자진행실험실검험급영상학검사.진이제취환인급기친속외주혈기인조DNA,채용침대조직비특이성감성린산매ALPL기인조공구급편마구적특이성인물진행PCR확증,직접대산물진행측서,병대소감정적돌변재무관인군중진행험증.결과 환인혈감성린산매수평현저강저,동시존재고개혈증、중도빈혈급쌍신개화；골격구유구루병양개변.ALPL기인측서결과현시환인위복합잡합돌변,동시휴대위우제7외현자적c.814C ＞T (p.R272C)착의돌변급위우제9외현자적c.1101_1103 delCTC (p.S368 del)감기결실돌변.림상표현정상적환인모친、부친위잡합자,분별휴대c.1101_1103 delCTC (p.S368del)감기결실돌변급c.814C ＞T (p.R272C)착의돌변.해가계부합상염색체은성유전,50례무관건강개체험증미발현상술량충돌변존재.결론 ALPL기인c.814C＞T(p.R272C)화c.1101_1103 delCTC(p.S368del)돌변여해가계영인형저린산매혈증림상표현밀절상관.
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.S368del) 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.