PMC10326848_01
Clinical and radiographic findings at different ages (A-C): Facial features of patient 1 at 4.5 and 30 years. Note broad and prominent forehead, sparse anterior hairline and medial eyebrows, prominent eyes, epicanthal folds, hypertelorism, telecanthus, depressed nasal root, bulbous nasal tip, prognathism, malar flattening, thin upper lip vermilion and mildly posteriorly rotated ears. (D-I): Radiographic examination of patient 1 showed mild dolichocephaly with frontal bossing, dolichospondyly, a mildly narrow thorax, gracile long bones, and flat capital femoral epiphyses. The elbow joint was dislocated. (J-L): Facial features of patient 2 at 7 and 49 years. Note hypertelorism with telecanthus, down slanting palpebral fissures, depressed nasal bridge, maxillary hypoplasia, broad and prominent forehead, mildly posteriorly rotated ears and short neck. The photographs are published with informed signed consents from both patients. (M-Q): Radiographic examination of patient 2 showed dolichocephaly with frontal bossing, dolichospondyly, a narrow thorax with glenoid dysplasia, gracile ulna and radius and hip dysplasia. The computer tomography of the lumbar spine radiograms showed spondylosis and spinal canal stenosis with posterior scalloping of the vertebral bodies. The radiograms of the hip joints showed advanced degenerative joint disease along with subluxation of the left. The femoral heads were small, and the femoral necks were short.
fgene-14-1174046-g001.jpg
PMC10326848_02_fgene-14-1174046-g001.jpg
F1
The patient has distinct craniofacial features (Figure 1) and redundant umbilical skin. The lumbar spine showed spondylosis and spinal canal stenosis with posterior scalloping of the vertebral bodies (Figure 1). Figure S1). Further, we extracted genes within the inversion, as well as genes in the region chr6:1,000,000-11,000,00; yielding 39 genes within the inversion, 11 genes downstream, and 3 genes upstream of the inversion (Supplementary Information S1).
PMC10326848_02
Clinical and radiographic findings at different ages (A-C): Facial features of patient 1 at 4.5 and 30 years. Note broad and prominent forehead, sparse anterior hairline and medial eyebrows, prominent eyes, epicanthal folds, hypertelorism, telecanthus, depressed nasal root, bulbous nasal tip, prognathism, malar flattening, thin upper lip vermilion and mildly posteriorly rotated ears. (D-I): Radiographic examination of patient 1 showed mild dolichocephaly with frontal bossing, dolichospondyly, a mildly narrow thorax, gracile long bones, and flat capital femoral epiphyses. The elbow joint was dislocated. (J-L): Facial features of patient 2 at 7 and 49 years. Note hypertelorism with telecanthus, down slanting palpebral fissures, depressed nasal bridge, maxillary hypoplasia, broad and prominent forehead, mildly posteriorly rotated ears and short neck. The photographs are published with informed signed consents from both patients. (M-Q): Radiographic examination of patient 2 showed dolichocephaly with frontal bossing, dolichospondyly, a narrow thorax with glenoid dysplasia, gracile ulna and radius and hip dysplasia. The computer tomography of the lumbar spine radiograms showed spondylosis and spinal canal stenosis with posterior scalloping of the vertebral bodies. The radiograms of the hip joints showed advanced degenerative joint disease along with subluxation of the left. The femoral heads were small, and the femoral necks were short.
fgene-14-1174046-g001.jpg
PMC10326848_02_fgene-14-1174046-g001.jpg
F1
The patient has distinct craniofacial features (Figure 1) and redundant umbilical skin. The lumbar spine showed spondylosis and spinal canal stenosis with posterior scalloping of the vertebral bodies (Figure 1). Figure S1). Further, we extracted genes within the inversion, as well as genes in the region chr6:1,000,000-11,000,00; yielding 39 genes within the inversion, 11 genes downstream, and 3 genes upstream of the inversion (Supplementary Information S1).
Molecular findings: (A) Schematic representation of the complex rearrangement and confirmation of the 5 breakpoint (BP1) using Sanger sequencing in patient 1 and in a normal control DNA sample. Complex genomic rearrangement includes: 4.9 kb deletion including FOXC1 followed by an inversion of approximately 7 MB and a 7.1 kB deletion. Primer pairs used for amplification and sequencing of the breakpoints 1 (BP1) were P1F and P1R. For amplification of the normal control sequence corresponding to the position of BP1 we used primer pairs P1F and P3R. (B) Genome and Sanger sequencing of DNA sample from patient 2 showing stop-gain variant in FOXC1 (NM_001453.3):c.467del, p.(Pro156Argfs*25).
fgene-14-1174046-g002.jpg
PMC10326848_02_fgene-14-1174046-g002.jpg
F2
The breakpoint 1 was confirmed using Sanger sequencing (Figure 2A). String network analysis showed a network with significantly more interactions than expected (p < 1.0e-16), indicating the disruption of gene clusters (Supplementary Figure S2). Genome sequencing (GS) (NGS; Illumina 2500, Agilent Sure Select) performed as described previously revealed a heterozygous single nucleotide deletion in FOXC1 Hg19 NC_000006.11(NM_001453.3): c.467del, p.(Pro156Argfs*25), (Hg38 NC_000006.12(NM_001453.3):c.467del), which was confirmed with Sanger sequencing (Figure 2B).