摘要目的:对1例孤独症谱系障碍合并45，X/46，XY嵌合体患者进行基因检测。方法:抽取家系的血液标本提取DNA进行全外显子测序(whole exome sequencing，WES)筛选可疑致病性变异位点，并应用Sanger测序方法对变异位点进行验证。结果:检测到先证者中孤独症谱系障碍相关基因 CACNA1I基因c.4781G>A(p.Arg1594Gln)的错义变异。染色体数目变异相关基因 MTRR基因c. 268C>T (p.Arg90Trp)的新发错义变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南， CACNA1I基因c. 4781G>A(p.Arg1594Gln)变异判定为致病性变异(PVS1，PM1，PM2，PP3)。 MTRR基因c. 268C>T (p.Arg90Trp)判定为意义不明的变异。 结论:MTRR基因c.268C>T (p.Arg90Trp)和 CACNA1I基因c.4781G>A(p.Arg1594Gln)可能是患者性染色体数目变异和孤独症谱系障碍的风险基因。

abstractsObjective:To carry out genetic testing for a patient with 45, X/46, XY mosaicism and autism spectrum disorder (ASD).Methods:Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter.Results:The proband and his father were found to harbor a heterozygous c. 4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c. 268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c. 4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c. 268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance. Conclusion:Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.