PMC6281661_01
The pedigree and the brain images.. a Pedigree of the family. Arrow indicates the proband. b Brain computed tomography images (Upper) and a T2-weighted magnetic resonance image (Lower) of the patient. Prominent cerebellar hypoplasia, an enlarged fourth ventricle and posterior fossa, and ventriculomegaly were noted
41439_2018_32_Fig1_HTML.jpg
PMC6281661_01_41439_2018_32_Fig1_HTML.jpg
Fig1
His maternal uncle was affected with hydrocephalus (Fig. 1a). Brain computed tomography (CT) and brain magnetic resonance imaging (MRI) suggested DWM (Fig. 1b). We narrowed the breakpoint region to a 437-bp PCR product amplified by a set of PCR primers derived from intron 10 and intron 15 (Supplementary Fig. 1).
Identification of an intragenic deletion in
OPHN1
in the patient III-1.
a Agarose gel image of the PCR products corresponding to intron 10, exon 12, and intron 15 in OPHN1 in the patient and his mother (II-2). Exon 12 in the patient was deleted. The genomic structure of OPHN1 is also shown in the agarose gel image of each PCR analysis. P positive control DNA from an unaffected person, N negative control (H2O), M 100-bp ladder DNA size marker. b (Upper) the deletion map of OPHN1. The green rectangle with end bars shows the deleted region. The deletion encompasses 13.5 kb from intron 10 to intron 15. (Lower) The region proximal to the deletion, shown as a red bar, and the region distal to the deletion, shown as a blue bar. Sequence chromatograms of the junction fragment containing the breakpoint site from the patient and his mother are shown in the middle two rows. An overlap of a five-nucleotide motif (AATTA) is shown as a pink bar. Reference sequences of the corresponding regions in intron 10 (upper) and intron 15 (lower) are shown
41439_2018_32_Fig2_HTML.jpg
PMC6281661_01_41439_2018_32_Fig2_HTML.jpg
Fig2
Consequently, we found an intragenic deletion in OPHN1 involving exon 11-15, which include the PH and GAP domains (Fig. 2a). No low copy repeats or segmental duplications were found adjacent to the deletion breakpoints, suggesting that the genomic rearrangement occurred by a microhomology-mediated mechanism and not by non-allelic homologous recombination (Fig. 2b).