一例罕见的Chediak-Higashi综合征患儿的基因型及表型分析

Identification of novel variants in a Chinese patient with Chediak-Higashi syndrome

目的探讨Chediak-Higashi综合征(Chediak-Higashi syndrome,CHS)基因变异与临床症状之间的相关性。方法通过全外显子组测序,结合临床表现和辅助检查结果,分析一例先证者的致病原因。结果先证者临床表现为部分皮肤白化合并色素异常沉着、反复感染、轻度贫血及易淤伤等。基因检测结果显示先证者为LYST基因c.2437C>T(p.Arg813*)和c.6077dupA(p.Tyr2026fs)(NM_000081)复合杂合变异所致的CHS患者,其父母分别为上述变异的携带者。两个变异既往均未见报道。基因型与表型的相关性分析提示,临床表型严重CHS的基因变异多发于HEAT repeats结构域(81.6%),而在PH_BEACH结构域未发现变异。结论本研究丰富了CHS相关的LYST基因变异谱,并为临床诊断、产前诊断和预后评估提供了依据,为明确LYST在囊泡运输过程的分子机制提供了新的线索。

Objective To explore the genetic basis for a child featuring Chediak-Higashi syndrome(CHS).Methods Clinical manifestations and results of auxiliary examination of the proband were analyzed.The proband was subjected to whole exome sequencing,and the results were verified by Sanger sequencing.Correlation between the genotype and clinical phenotype was analyzed.Results The proband showed partial skin albinism,recurrent respiratory infection and other immune deficiencies.Genetic testing showed that he has harbored c.2437C>T(p.Arg813*)and c.6077dupA(p.Tyr2026fs)(NM_000081)compound heterozygous variants of the LYST gene,for which his parents were both carriers.Neither variant was reported previously.HEAT repeats domain was frequently associated with more severe phenotype of CHS(81.6%),whilst no variant has been found in the PH_BEACH domain.Conclusion This study has enriched the spectrum of LYST gene variants associated with CHS and enabled clinical diagnosis,prenatal diagnosis and prognostic evaluation for the child.