Figure 3
Identified mutation in a family with microcephaly.
(a) Family tree of the pedigree with microcephaly. Shaded symbols denote affected individuals. Asterisks denote NGS was performed. (b) Sagittal T1-weighted brain magnetic resonance image (MRI) of the II-2 individual at 4 years of age shows frontal sloping and reduced volume of the brain, particularly the frontal lobe of the cerebrum. (c) Filtering the candidate mutations for the II-2 individual. The numbers in parenthesis represent the number of called variants with CCCS. Overlapping variants between WES and CCCS are not excluded. The other individuals are shown in Supplementary Fig. S3. The top row shows the variant counts called by ‘WES’ and ‘WES and CCCS’. The second row shows counts after excluding known variants found in databases, except for known pathogenic mutations. The third row shows variant counts after excluding synonymous changes. Finally, the last raw of variant counts is consistent with the phenotype in the pedigree (i.e., total number of the autosomal recessive and compound heterozygous variants). (d) ASPM gene in human genome. Gray and black box indicate exonic untranslated regions (UTR) and CDS regions respectively. Red triangles indicate loci of identified mutation. Blue arrow (<<) indicates the coding direction. (e) Domains and mutations in the ASPM protein. Red pins indicate loci of known nonsense mutations in HGMD and ClinVar databases at 2014 June. Red triangles indicate loci of identified mutation. Orange pentagon, black hexagon, green hexagon and magenta oval denote calponin homology (IPR001715: InterPro ID), calmodulin-regulated spectrin-associated protein CH (IPR022613), P-loop containing nuclease triphosphate hydrolase (IPR027417) and armadillo-type hold domain (IPR016024), respectively. Blue oval denotes IQ motif, EF-hand binding site (IPR0000048). (f) Sanger sequencing data of the identified mutation.
