PMC9630465_01
Phenotype and genotype of index patients with ARHGEF17 mutation (A) Pedigree of index family indicating affected patients (III.2, III.3). (B) Photomicrographs of III.2 and III.3. (C) MRI images of III.2 revealed general atrophy/hypoplasia of the brain parenchyma, enlarged ventricular system (thin arrows) and thin, but complete corpus callosum (arrow heads), chronic ischemic changes periventricular white matter surrounding occipital horns, moderate cerebral atrophy and thickened scull bone (thick arrows). (D) Schematic representation of ARHGEF17 cDNA with 21 exons and the wild-type ARHGEF17 protein with the identified variants of our index family (black) and previously reported homozygous variants (gray). A homozygous exchange of a single base C to T in exon 1 of the ARHGEF17 (c.1624C>T (NM_014786.4), p.R542W (NP_055601.2) was identified and confirmed through Sanger sequencing. (E) Electropherogram traces depicting the exchange of C to T at position 1624 of the ARHGEF17 gene. (F) The site of mutation is located in DCLK1 consensus site [LRRAKSF (green)] of ARHGEF17 and it is highly conserved across species.
fneur-13-1017654-g0001.jpg
PMC9630465_02_fneur-13-1017654-g0001.jpg
F1
Proband 2 (P2, III.3) was a 22-year-old male born at term with normal birth weight and length (Figures 1A,B, Table 1). T in exon 1 of the ARHGEF17 gene (Chr 11:73021307, hg19/GRCh37, c.1624C>T, NM_014786.4; p.R542W, NP_055601.2) in two affected siblings (III.2 and III.3) (Figure 1D) and confirmed the mutation by Sanger sequencing (Figure 1E). The identified variant lies in a protein region highly conserved across species (Figure 1F). The variant is disease-causative in nature, as predicted by Mutation Taster and SIFT (https://www.mutationtaster.org/, http://genetics.bwh.harvard.edu/pph2/, https://sift.bii.a-star.edu.sg).
PMC9630465_02
Phenotype and genotype of index patients with ARHGEF17 mutation (A) Pedigree of index family indicating affected patients (III.2, III.3). (B) Photomicrographs of III.2 and III.3. (C) MRI images of III.2 revealed general atrophy/hypoplasia of the brain parenchyma, enlarged ventricular system (thin arrows) and thin, but complete corpus callosum (arrow heads), chronic ischemic changes periventricular white matter surrounding occipital horns, moderate cerebral atrophy and thickened scull bone (thick arrows). (D) Schematic representation of ARHGEF17 cDNA with 21 exons and the wild-type ARHGEF17 protein with the identified variants of our index family (black) and previously reported homozygous variants (gray). A homozygous exchange of a single base C to T in exon 1 of the ARHGEF17 (c.1624C>T (NM_014786.4), p.R542W (NP_055601.2) was identified and confirmed through Sanger sequencing. (E) Electropherogram traces depicting the exchange of C to T at position 1624 of the ARHGEF17 gene. (F) The site of mutation is located in DCLK1 consensus site [LRRAKSF (green)] of ARHGEF17 and it is highly conserved across species.
fneur-13-1017654-g0001.jpg
PMC9630465_02_fneur-13-1017654-g0001.jpg
F1
Proband 2 (P2, III.3) was a 22-year-old male born at term with normal birth weight and length (Figures 1A,B, Table 1). T in exon 1 of the ARHGEF17 gene (Chr 11:73021307, hg19/GRCh37, c.1624C>T, NM_014786.4; p.R542W, NP_055601.2) in two affected siblings (III.2 and III.3) (Figure 1D) and confirmed the mutation by Sanger sequencing (Figure 1E). The identified variant lies in a protein region highly conserved across species (Figure 1F). The variant is disease-causative in nature, as predicted by Mutation Taster and SIFT (https://www.mutationtaster.org/, http://genetics.bwh.harvard.edu/pph2/, https://sift.bii.a-star.edu.sg).