loading page

Genomic analysis of Korean patients with microcephaly
  • +5
  • Jiwon Lee,
  • Jong Eun Park,
  • Chung Lee,
  • Ah Reum Kim,
  • Byung Joon Kim,
  • Woong Yang Park,
  • Chang-Seok Ki,
  • Jeehun Lee
Jiwon Lee
Samsung Medical Center
Author Profile
Jong Eun Park
Hanyang University Guri Hospital
Author Profile
Chung Lee
Samsung Genome Institute
Author Profile
Ah Reum Kim
Samsung Medical Center
Author Profile
Byung Joon Kim
Samsung Medical Center
Author Profile
Woong Yang Park
Samsung Genome Institute
Author Profile
Chang-Seok Ki
GC Genome
Author Profile
Jeehun Lee
Samsung Medical Center
Author Profile

Abstract

Microcephaly is a prevalent phenotype of the patients with neurodevelopmental problems, often with genetic causes. We comprehensively investigated the clinical phenotypes and genetic background of microcephaly in Korean patients. We enrolled 40 patients with microcephaly. We analyzed clinical phenotypes and radiologic images and conducted whole exome sequencing (WES) and an 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 already known to be related to microcephaly in 12 patients (30%); nine of these were de novo variants with autosomal dominant inheritance. Two unrelated patients had mutations in the KMT2A gene. In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes. Seven patients (17.5%) were diagnosed as having pathogenic CNVs. Korean patients with microcephaly show a different genetic spectrum from that of patients with microcephaly of other ethnicities. WES with a CNV analysis represents an effective approach for diagnosing the underlying causes of microcephaly.