本文選題：GLDC基因　切入點(diǎn)：復(fù)合雜合突變　出處：《中國(guó)當(dāng)代兒科雜志》2017年10期

【摘要】：非酮性高甘氨酸血癥(NKH)是由甘氨酸裂解系統(tǒng)缺陷引起的常染色體隱性遺傳疾病,分經(jīng)典型和非經(jīng)典型,而非經(jīng)典型表現(xiàn)復(fù)雜多樣,診斷較為困難。該文報(bào)道1個(gè)NKH家系,父母表型正常,兄妹均非新生兒期起病,哥哥表現(xiàn)為難治性癲vN、嚴(yán)重的雙側(cè)痙攣性癱瘓和智力低下,血和腦脊液的甘氨酸濃度增高,尿甘氨酸與肌酐的比值增高,腦脊液與血甘氨酸濃度的比增高;妹妹表現(xiàn)為語(yǔ)言發(fā)育遲緩、共濟(jì)失調(diào)、舞蹈病和發(fā)熱誘發(fā)的精神行為異常和肌張力減退,腦脊液甘氨酸濃度增高、腦脊液與血甘氨酸濃度比增高。高通量測(cè)序提示兄妹均存在GLDC基因母源c.3006CG(p.C1002W)錯(cuò)義突變和父源c.1256CG(p.S419X)無(wú)義突變,生物學(xué)軟件預(yù)測(cè)均提示致病突變。轉(zhuǎn)染兩種突變體GLDC基因的H293T細(xì)胞甘氨酸脫羧酶活性均有下調(diào)。NKH表型多樣,二代高通量測(cè)序有利于疑似病例的確認(rèn),非經(jīng)典N(xiāo)KH與基因突變導(dǎo)致的甘氨酸脫羧酶活性下調(diào)相關(guān)。
[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.

【作者單位】： 浙江大學(xué)醫(yī)學(xué)院附屬兒童醫(yī)院腦電圖室;浙江大學(xué)醫(yī)學(xué)院附屬兒童醫(yī)院神經(jīng)內(nèi)科;浙江大學(xué)醫(yī)學(xué)院附屬兒童醫(yī)院遺傳代謝科;
【基金】：浙江省省級(jí)科技項(xiàng)目(2012C33101)
【分類(lèi)號(hào)】：R725.9

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