GLDC基因复合杂合突变致非经典型非酮性高甘氨酸血症家系的临床和遗传学分析

发布时间：2018-04-09 03:14

本文选题：GLDC基因　切入点：复合杂合突变　出处：《中国当代儿科杂志》2017年10期

【摘要】：非酮性高甘氨酸血症(NKH)是由甘氨酸裂解系统缺陷引起的常染色体隐性遗传疾病,分经典型和非经典型,而非经典型表现复杂多样,诊断较为困难。该文报道1个NKH家系,父母表型正常,兄妹均非新生儿期起病,哥哥表现为难治性癫vN、严重的双侧痉挛性瘫痪和智力低下,血和脑脊液的甘氨酸浓度增高,尿甘氨酸与肌酐的比值增高,脑脊液与血甘氨酸浓度的比增高;妹妹表现为语言发育迟缓、共济失调、舞蹈病和发热诱发的精神行为异常和肌张力减退,脑脊液甘氨酸浓度增高、脑脊液与血甘氨酸浓度比增高。高通量测序提示兄妹均存在GLDC基因母源c.3006CG(p.C1002W)错义突变和父源c.1256CG(p.S419X)无义突变,生物学软件预测均提示致病突变。转染两种突变体GLDC基因的H293T细胞甘氨酸脱羧酶活性均有下调。NKH表型多样,二代高通量测序有利于疑似病例的确认,非经典NKH与基因突变导致的甘氨酸脱羧酶活性下调相关。
[Abstract]:NKH (NKH) is caused by a defective glycine cleavage system of autosomal recessive genetic disease, divided into classical and non classical type, and non classical features are complex, it is difficult to diagnose. This paper reported 1 NKH families and their parents were phenotypically normal siblings were non neonatal onset, brother performance refractory epilepsy vN, severe bilateral spastic paralysis and mental retardation, glycine concentration in blood and cerebrospinal fluid was increased and the ratio of urinary creatinine and glycine in cerebrospinal fluid and blood glycine concentration ratio increases; the performance of language sister with developmental delay, ataxia, mental disease and fever induced by abnormal and muscle tension. Loss of glycine concentration in cerebrospinal fluid increased, cerebrospinal fluid and blood concentration of glycine than increased. High throughput sequencing suggested that there were GLDC gene and maternal c.3006CG (p.C1002W) and paternal c.1256CG missense mutation (p.S419X) Nonsense mutations, biology software prediction showed mutations. H293T cells were transfected with two kinds of glycine decarboxylase activity of mutant GLDC gene down-regulation of.NKH phenotypic diversity, the two generation of high-throughput sequencing to confirm suspected cases, non classical NKH and gene mutation of glycine decarboxylase activity leads to down-regulation.

【作者单位】：浙江大学医学院附属儿童医院脑电图室;浙江大学医学院附属儿童医院神经内科;浙江大学医学院附属儿童医院遗传代谢科;
【基金】：浙江省省级科技项目(2012C33101)
【分类号】：R725.9

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