PMC5938052_01
a Fetal brain magnetic resonance imaging (MRI) at 32 weeks of gestation. An axial half-Fourier-acquired single-shot turbo spin echo (HASTE) image shows ventriculomegaly and a large cleft in the right cerebral hemisphere. b Brain MRI on day 1. An axial T2-weighted image shows a large right hemispheric cleft lined by abnormal gray matter with ventriculomegaly. This is characteristic of schizencephaly
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Fig1
A fetal brain MRI at 32 weeks of gestation showed bilateral ventriculomegaly and an enlarged right cerebral hemisphere cleft (Fig. 1a). T2-weighted images, which suggested multiple recurrent bleeds and damage in the bilateral basal ganglia and ventricle wall (Fig. 1b).
a Sequence electropherogram for COL4A1 in the patient and parents. A de novo event was identified in this study. b Sequence electropherogram. The amplified PCR product was cloned into the pCR4-TOPO vector and each clone was subjected to sequencing. The two base substitutions are indicated on the same allele. c A novel heterozygous mutation in COL4A1 (NM_001845.5; c.2645_2646delinsAA, p.Gly882Glu) was identified in the patient. The COL4A1 protein contains 13 repeating (Gly-X-Y)n amino acid sequences, as registered in InterPro (https://www.ebi.ac.uk/interpro/). The amino acid sequences are highlighted with red boxes (amino acid positions 46-160, 172-221, 275-331, 474-532, 541-590, 690-735, 743-796, 839-895, 885-937, 948-1005, 999-1056, 1058-1116, and 1384-1440). d A mutation at an evolutionarily conserved amino acid in nine species. Amino acid position 882 in the COL4A1 protein is highlighted by a gray box
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Fig2
Sanger sequencing confirmed that this variant occurred as a de novo event (Fig. 2a). The cloned DNA sequence was confirmed by Sanger sequencing, with two base substitutions identified on the same allele (Fig. 2b). The amino acid substitution (p.Gly882Glu) was localized in the collagen triple-helix domain, which consists of a repeating (Gly-X-Y)n amino acid sequence and is evolutionarily conserved among different species (Fig. 2c, d).