Kim Dohyung, Yoon Ji-Hee, Bae Hyunwoo, Hwang Soojin, Seo Go Hun, Koh June-Young, Ju Young Seok, Do Hyo-Sang, Kim Soyoung, Choi In Hee, Kim Gu-Hwan, Kim Ja Hye, Choi Jin-Ho, Lee Beom Hee
Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Medical Genetics Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
J Hum Genet. 2025 May;70(5):243-248. doi: 10.1038/s10038-025-01325-1. Epub 2025 Feb 25.
The Verloes or Hale diagnostic criteria have been applied for diagnosing CHARGE syndrome in suspected patients. This study was conducted to evaluate the diagnostic rate of CHD7 according to these diagnostic criteria in suspected patients and also to investigate other genetic defects in CHD7-negative patients. The clinical findings and the results of genetic testing of CHD7, chromosome microarray, exome sequencing, or genome sequencing of 59 subjects were reviewed. CHD7 pathogenic variants were identified in 78% of 46 subjects who met either the Verloes or Hale diagnostic criteria and in 87% of 38 subjects who met both criteria, whereas no CHD7 variant was detected in 13 subjects who met neither criterion. Among 23 patients without the CHD7 variant, six genetic diseases were identified in 7 patients, including Wolf-Hirschhorn syndrome, 1q21 deletion syndrome, 19q13 microdeletion, and pathogenic variants in PLCB4, TRRAP, and OTX2. Based on these comprehensive analyses, the overall diagnostic rate was 73% for seven different genetic diseases. This study emphasizes the importance of comprehensive clinical and genetic evaluation in patients with clinically suspected CHARGE syndrome, recognizing the overlapping phenotypes in other rare genetic disorders.
Verloes或Hale诊断标准已应用于疑似CHARGE综合征患者的诊断。本研究旨在根据这些诊断标准评估疑似患者中CHD7的诊断率，并调查CHD7阴性患者中的其他基因缺陷。回顾了59名受试者的临床发现以及CHD7的基因检测结果、染色体微阵列、外显子组测序或基因组测序结果。在符合Verloes或Hale诊断标准的46名受试者中，78%鉴定出CHD7致病变体；在符合两项标准的38名受试者中，87%鉴定出CHD7致病变体；而在不符合任何一项标准的13名受试者中未检测到CHD7变体。在23名无CHD7变体的患者中，7名患者鉴定出6种遗传疾病，包括Wolf-Hirschhorn综合征、1q21缺失综合征、19q13微缺失以及PLCB4、TRRAP和OTX2中的致病变体。基于这些综合分析，7种不同遗传疾病的总体诊断率为73%。本研究强调了对临床疑似CHARGE综合征患者进行全面临床和基因评估的重要性，同时认识到其他罕见遗传疾病中存在重叠表型。
