低碱性磷酸酶血症一家系临床与基因分析  

Clinical and genetic analysis of a family with low alkaline phosphatase

作　　者：卢维城[1] 石聪聪[2] 蔡东 郑旭[1] 郝虎[2] 肖昕[2] LU Weicheng;SHI Congcong;CAI Dong;ZHENG Xu;HAO Hu;XIAO Xin(Department of Neonatology, Hainan People’s Hospital, Haikou 570311, Hainan, China;Department of Pediatrics, The Sixth Affiliated Hospital of SunYat-Sen University, Guangzhou 510655, Guangdong, China)

机构地区：[1]海南省人民医院新生儿科,海南海口570311 [2]中山大学附属第六医院儿科,广东广州510655

出　　处：《临床儿科杂志》2017年第9期682-686,共5页Journal of Clinical Pediatrics

摘　　要：目的探讨组织非特异性碱性磷酸酶(TNSALP)基因检测在低碱性磷酸酶血症(HPP)产前诊断中的作用。方法回顾分析1例新生儿HPP患儿的临床资料,以及全外显子组测序检测TNSALP基因结果;采集家系成员外周血,及患儿母亲第2胎孕17周胎儿的羊水细胞,进行候选基因突变的Sanger测序验证。结果患儿,男性、6日龄,主要表现为多发性骨折,肢体缩短弯曲,呼吸困难,生后9天死于呼吸衰竭;血清碱性磷酸酶下降,血钙轻度下降,血磷正常,血清25羟维生素-D和甲状旁腺激素均正常;X线显示全身骨骼严重矿化不良,长骨干骺端增大呈杯口状,多发性骨折;基因测序结果显示患儿TNSALP基因存在一复合杂合性错义突变,分别为位于第6外显子内的杂合性错义突变c.542C>T导致第181位氨基酸由丝氨酸突变为亮氨酸(p.S181L),第10外显子内杂合性错义突变c.1016G>A导致第339位氨基酸甘氨酸突变为谷氨酸(p.G339E);患儿父母表型均正常,c.542C>T突变遗传自父亲,c.1016G>A突变遗传自母亲。胎儿未检出这两种突变。结论 TNSALP基因分析可应用于HPP的诊断以及产前诊断。Objective To investigate the role of TNSALP gene detection in prenatal diagnosis of HPP.Method The clinical data and the results of complete exon sequencing of TNSALP gene in one neonate with low alkaline phosphatase(HPP)were analyzed retrospectively.Peripheral bloods from his family members were collected.The amniotic fluid cell in fetuses at17weeks was tested for candidate gene mutations by Sanger sequencing.Results Mainly manifestations in6-day-old baby were multiple fractures,limb shortening and bending and dyspnea.He died of respiratory failure9days after birth.The serum alkaline phosphatase was decreased and serum calcium was decreased slightly;serum phosphorus,serum25hydroxyvitamin-D and parathyroid hormone were normal.X-ray showed that the whole body bone was very poorly mineralized,and the long diaphysis was enlarged with shape of a cup at the end and multiple fractures existed.Gene sequencing revealed a complex heterozygous missense mutation in the TNSALP gene,including the heterozygous missense mutation c.542C>T in exon sixth causing181st amino acids changed from serine to leucine(p.S181L),and tenth exon heterozygous missense mutation in c.1016G>A causing339th amino acid changed from glycine to glutamic acid(p.G339E).The parental phenotypes were normal.The c.542C>T mutation is inherited from his father and the c.1016G>A mutation is inherited from his mother.These two mutations were not detected in the fetus.Conclusion TNSALP gene analysis can be applied to the diagnosis and prenatal diagnosis of HPP.

关 键 词：低碱性磷酸酶血症 组织非特异性碱性磷酸酶基因 突变 产前诊断 

分 类 号：R722.1[医药卫生—儿科]