Gug Cristina, Gorduza Eusebiu Vlad, Lăcătuşu Adrian, Vaida Monica Adriana, Bîrsăşteanu Florin, Puiu Maria, Stoicănescu Dorina
Department of Microscopic Morphology, Victor Babeş University of Medicine and Pharmacy, 300041 Timisoara, Romania.
Prenatal Diagnosis Department, Cuza Voda Obstetrics-Gynecology Clinical Hospital, 700038 Iasi, Romania.
Exp Ther Med. 2020 Jul;20(1):479-485. doi: 10.3892/etm.2020.8683. Epub 2020 Apr 23.
CHARGE syndrome is an autosomal dominant condition caused by mutations in the chromodomain helicase DNA binding protein 7 (CHD7) gene. The present study reported on the case of a 16-month-old female with plurimalformative syndrome, whose etiology was identified by clinical whole-exome sequencing (WES) analysis. Clinical and follow-up assessments identified multiple craniofacial dysmorphisms, congenital defects and functional symptoms, including dysphagia and Marcus Gunn jaw winking synkinesis. Trio-WES analysis was performed for the patient and their parents and the presence of CHARGE syndrome was further indicated using single-molecule real-time sequencing. A pathogenic variant, c.4379_4380del (p.Ile1460Argfs15), was identified in exon 19 of the CHD7 gene, which resulted in a premature translational stop signal. Trio-WES analysis was used for further investigation, indicating that neither of the patient's parents had the mutation and confirming its nature. To the best of our knowledge, the case of the present study was the first reported case of CHARGE syndrome in Romania with congenital defects including an aberrant right subclavian artery and a horseshoe kidney. CHARGE syndrome was diagnosed in the patient based on the pathogenic mutation in the CHD7 gene. To the best of our knowledge, the present case report is the first to suggest that the CHD7 gene variant is associated with CHARGE syndrome.
CHARGE综合征是一种常染色体显性疾病，由染色质结构域解旋酶DNA结合蛋白7（CHD7）基因突变引起。本研究报告了一例16个月大患有多种发育异常综合征的女性病例，其病因通过临床全外显子组测序（WES）分析得以确定。临床及随访评估发现了多种颅面畸形、先天性缺陷及功能症状，包括吞咽困难和马库斯·冈恩下颌瞬目联动。对该患者及其父母进行了三联体WES分析，并使用单分子实时测序进一步证实了CHARGE综合征的存在。在CHD7基因第19外显子中鉴定出一个致病变体c.4379_4380del（p.Ile1460Argfs15），该变体导致翻译提前终止信号。通过三联体WES分析进一步研究表明，患者的父母均无此突变，从而确定了该突变的性质。据我们所知，本研究病例是罗马尼亚首例报告的CHARGE综合征病例，伴有包括右锁骨下动脉异常和马蹄肾在内的先天性缺陷。基于CHD7基因中的致病突变，该患者被诊断为CHARGE综合征。据我们所知，本病例报告首次表明CHD7基因变体与CHARGE综合征有关。
