可报告的序列变异都是目视检查确认的对齐。以下工具被用于in-silico功能预测(突变品酒师:疾病突变;Polyphen2筛选)。c的变体。839C>T was predicted as damaging and was classified as likely to be pathogenic. Sanger sequencing was done to confirm the presence of the variants in family members. It was confirmed that the child was hemizygous and the mother was heterozygous for the variant (Figure
1)。他被诊断为临床x连锁精神retardation-hypotonic相综合症。
三人外显子组测序后进行渊源者和父母相同的协议。错义变体ATRX: c。5369C>T, p. Ala1790Val was found in the heterozygous state in the mother and in hemizygous state in the proband. The results were confirmed using bi-directional genomic sequencing using a familial positive control for the sequence variant. Methylation analysis was also performed using a previously described protocol [
9]。渊源者显示完成X失活和高度倾斜X-inactivation渊源者的母亲。放大的结果从消化和病人的母亲nondigested DNA显示高度倾斜X-inactivation(非随机的)。中这是一个常见的发现x连锁精神发育迟滞女性运营商确认使用人类的雄激素受体(AR)基因位于Xq11.2。人类AR基因包含一个高度多态在坐标系CAG重复编码11-31甘氨酸残基基因的外显子1 (
10]。
到目前为止,在变异的报道
ATRX基因与x染色体相关精神retardation-hypotonic相综合征(
https://www.omim.org/entry/300032 41)这里描述的两个变量是没有报告。第一个变种c.839C > T | p。Cys280Tyr位于外显子9的
ATRX基因。这种变体引起非保守的氨基酸替换,即。,substitution of Cysteine by Tyrosine that may result in a significant alteration of the structure of the protein. As it lies in the ADD domain this nonconservative amino acid substitution is likely to be pathogenic [
11]。集群ATRX突变主要发生在ADD(50%)和解旋酶(30%)域(
7),这些与最高序列的区域保护人类和小鼠之间(图
2)。据报道,添加域突变与严重精神运动障碍和严重泌尿生殖异常。然而,我们的病人精神发育迟滞,但没有任何报道泌尿生殖异常。表型的比较(表
1),我们的病人的临床特征相关的ATRX-syndrome [
13]。
的复杂性疾病谱系表明ATRX可能参与调节其他未知的基因(
3]。第一个病人5相关的一般临床特征而第二个渊源者只有2的12 ATR-X综合症的主要临床特征。这些病人都是负α地中海贫血和HbH夹杂物被认为在87%的患者ATR-X [
13]。在硅片、功能预测工具,确定了c语言。839 c > T变体破坏性然而c。5369C>T was shown to have an uncertain clinical significance. There has been previous reports of mental retardation and epilepsy co-existing in patients with variants in
ATRX基因(
14]。这些情况下扩大ATR-X综合症的临床表现,为分子诊断开辟新的机会
ATRX突变的男性患者严重的全球发育迟缓和智障。