Lee Jiwon, Park Jong Eun, Lee Chung, Kim Ah Reum, Kim Byung Joon, Park Woong-Yang, Ki Chang-Seok, Lee Jeehun
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Department of Laboratory Medicine and Genetics, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, South Korea.
Front Genet. 2021 Jan 28;11:543528. doi: 10.3389/fgene.2020.543528. eCollection 2020.
Microcephaly is a prevalent phenotype in patients with neurodevelopmental problems, often with genetic causes. We comprehensively investigated the clinical phenotypes and genetic background of microcephaly in 40 Korean patients. We analyzed their clinical phenotypes and radiologic images and conducted whole exome sequencing (WES) and analysis of copy number variation (CNV). Infantile hypotonia and developmental delay were present in all patients. Thirty-four patients (85%) showed primary microcephaly. The diagnostic yield from the WES and CNV analyses was 47.5%. With WES, we detected pathogenic or likely pathogenic variants that were previously associated with microcephaly in 12 patients (30%); nine of these were variants with autosomal dominant inheritance. Two unrelated patients had mutations in the gene. In 10 other patients, we found mutations in the , and genes. Seven patients (17.5%) were diagnosed with pathogenic CNVs. Korean patients with microcephaly show a genetic spectrum that is different from that of patients with microcephaly of other ethnicities. WES along with CNV analysis represents an effective approach for diagnosis of the underlying causes of microcephaly.
小头畸形是神经发育问题患者中普遍存在的一种表型，通常由遗传因素引起。我们全面调查了40名韩国小头畸形患者的临床表型和遗传背景。我们分析了他们的临床表型和放射影像，并进行了全外显子组测序（WES）和拷贝数变异（CNV）分析。所有患者均有婴儿期肌张力减退和发育迟缓。34名患者（85%）表现为原发性小头畸形。WES和CNV分析的诊断率为47.5%。通过WES，我们在12名患者（30%）中检测到先前与小头畸形相关的致病性或可能致病性变异；其中9个是常染色体显性遗传变异。两名无亲缘关系的患者在该基因中发生了突变。在其他10名患者中，我们在、和基因中发现了突变。7名患者（17.5%）被诊断为致病性CNV。韩国小头畸形患者显示出与其他种族小头畸形患者不同的遗传谱。WES与CNV分析相结合是诊断小头畸形潜在病因的有效方法。
