低碱性磷酸酶血症一家系临床与基因分析

发布时间：2018-04-02 00:19

本文选题：低碱性磷酸酶血症　切入点：组织非特异性碱性磷酸酶基因　出处：《临床儿科杂志》2017年09期

【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.542CT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.1016GA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.542CT突变遗传自父亲,c.1016GA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。
[Abstract]:Objective to investigate the tissue nonspecific alkaline phosphatase (TNSALP) gene in low alkaline phosphatase (HPP) in prenatal diagnosis. Methods Retrospective analysis of clinical data of 1 cases of newborn children with HPP, and whole exome sequencing TNSALP gene detection results; family members including peripheral blood, and second mothers of children with fetal 17 weeks of gestation fetal amniotic fluid cells for Sanger sequencing of candidate gene mutation. The results were male, aged 6 days, mainly for multiple fractures, limb shortening bending, dyspnea, respiratory failure and died 9 days after birth; serum alkaline phosphatase decreased, serum calcium decreased slightly, blood phosphorus, serum 25 hydroxy vitamin -D and parathyroid hormone were normal; X-ray showed serious bone mineralization, metaphysis increases the cup shape, multiple fractures; gene sequencing results showed that children with TNSALP due to the existence of a compound heterozygous. The nonsense mutation, respectively located in the sixth exon of the heterozygous missense mutations in c.542CT cause 181st amino acid mutation by serine leucine (p.S181L), exon tenth in heterozygous missense mutations in c.1016GA cause 339th amino acid mutation of glycine to glutamic acid (p.G339E); parents of children with normal phenotype, c.542CT mutation is inherited from father, c.1016GA mutation inherited from the mother fetus. These two mutations were not detected. Conclusion TNSALP gene can be used in HPP diagnosis and prenatal diagnosis.

【作者单位】：海南省人民医院新生儿科;中山大学附属第六医院儿科;
【分类号】：R722.1

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