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.