全外显子组测序诊断1例罕见Chung-Jansen综合征

Diagnosis of a rare case of Chung-Jansen syndrome by whole exome sequencing

目的 探究1例智力障碍、发育迟缓患儿的致病原因。方法 患儿应用全外显子组测序技术(WES)和染色体拷贝数变异技术(CNV)筛选可疑致病性变异点,对家系采用Sanger测序方法对变异位点进行验证。结果 患儿CNV检测未发现100 kb以上已知的、明确致病的基因组拷贝数变异(CNVs)和染色体非整倍体,WES检测发现6q14.1染色体上PHIP基因(NM_017934.7:exon22:c.2537G>C:p.S846T)杂合错义突变,未见文献报道,父母均未携带此突变,根据美国医学遗传学与基因组学学会(ACMG)指南,PHIP基因c.2537G>C突变判断为疑似致病突变位点(PM2+PM6+PP2+PP3)。结论 PHIP基因c.2537G>C是导致患儿Chung-Jansen综合征疾病的原因,属于国内首例报道Chung-Jansen综合征疾病,为疾病临床诊断提供依据,在一定程度上补充了遗传学领域资料。

Objective To explore the cause of a child with intellectual disability and developmental delay. Methods Children patients were treated with whole exome sequencing(WES) technology and chromosome copy number variation(CNV)technology to screen the suspected pathogenic variants, and the pedigrees were treated with Sanger sequencing method to verify the variable sites. Results Copy number variation(CNV) detection of the children patients didn’t reveal the known and clearly pathogenic genome copy number variations(CNVs) and chromosome aneuploidy. Whole exome sequencing(WES)detected a heterozygous missense mutation in PHIP gene(NM_017934.7:exon22:c.2537G>C:p.S846T) on chromosome 6q14.1. No literature reports had been found. None of the patients carried the mutation. According to the guidelines of the American Academy of Medical Genetics and Genomics(ACMG), the c.2537G>C mutation of the PHIP gene was identified as a suspected pathogenic mutation site(PM2+PM6+PP2+PP3). Conclusion The PHIP gene c.2537G>C was the cause of Chung-Jansen syndrome in a child, which was the first reported disease of Chung-Jansen syndrome in China. It provided a basis for the clinical diagnosis of the disease and supplemented the data in the field of genetics to a certain extent.