A novel splice-site variant in the MCPH1 gene manifests with autosomal recessive primary microcephaly

Abstract

Autosomal recessive primary microcephaly is a rare neurodevelopmental disorder that results in severe microcephaly, reduction of brain volume, and mental retardation. Mutations in MCPH1, which encodes the protein microcephalin, have been detected in primary microcephaly. In this report, we describe an infant girl from a consanguineous Turkish family who is affected by autosomal recessive primary microcephaly. This patient also has craniofacial dysmorphic findings, intellectual disability, and developmental delay. Neuroimaging revealed a reduction in cranial volume and delayed myelination. We performed whole exome sequencing to find the genetic defects. A novel splice-site variant (NM_024596.5; MCPH1: c.321+5G > A) was identified in a homozygous state in intronic 4 of the MCPH1 gene. The parents of the proband were heterozygous carriers for this variation. This new splice site homozygous mutation in our patient will help to establish a database of genetic variants for populations. This study also enlarges the mutation spectrum of the MCPH1 gene and points out the importance of splice-site variants by sequencing.