PMC9024331_01
Clinical manifestations of the five RSTS cases. Positive findings of common RSTS characteristics, including distinctive facial features, and broadened thumbs and halluces, were noted in all of the enrolled cases. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5.
fgene-13-848879-g002.jpg
PMC9024331_05_fgene-13-848879-g002.jpg
F2
was a 4-year-old boy also with typical features of RSTS (Figure 2E).
Pedigrees and schematic summary of genetic alteration discoveries in this study. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5. WT, wild type.
fgene-13-848879-g003.jpg
PMC9024331_05_fgene-13-848879-g003.jpg
F3
Unexpectedly, WES also failed to identify pathogenic variants within the CREBBP and EP300 loci (Figure 3E).
MLPA and WES results for case 1. (A) MLPA of the proband showing heterozygous deletion at 16p13.3. (B) A visualization of the WES results for case 1 show fewer reads in the proband than in the healthy control, confirming the heterozygous deletion detected by MLPA.
fgene-13-848879-g004.jpg
PMC9024331_01_fgene-13-848879-g004.jpg
F4
TRAP1 and CREBBP (Figures 3A, 4A). To validate the results, we also performed WES on the proband's DNA, and a visualization of the WES results in IGV revealed low read coverage across the mutation span (Figure 4B).
PMC9024331_02
Clinical manifestations of the five RSTS cases. Positive findings of common RSTS characteristics, including distinctive facial features, and broadened thumbs and halluces, were noted in all of the enrolled cases. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5.
fgene-13-848879-g002.jpg
PMC9024331_05_fgene-13-848879-g002.jpg
F2
was a 4-year-old boy also with typical features of RSTS (Figure 2E).
Pedigrees and schematic summary of genetic alteration discoveries in this study. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5. WT, wild type.
fgene-13-848879-g003.jpg
PMC9024331_05_fgene-13-848879-g003.jpg
F3
Unexpectedly, WES also failed to identify pathogenic variants within the CREBBP and EP300 loci (Figure 3E).
Chromatograms of confirmative PCR-based Sanger sequencing and segregation analysis results. (A) A de novo nonsense CREBBP mutation in case 2. (B) A de novo CREBBP 2-bp deletion in case 3. (C) The CREBBP nonsense mutation was detected in both case 4 and the proband's mother.
fgene-13-848879-g005.jpg
PMC9024331_04_fgene-13-848879-g005.jpg
F5
Further segregation analysis showed that the mutation had occurred de novo (Figure 5C).
PMC9024331_03
Clinical manifestations of the five RSTS cases. Positive findings of common RSTS characteristics, including distinctive facial features, and broadened thumbs and halluces, were noted in all of the enrolled cases. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5.
fgene-13-848879-g002.jpg
PMC9024331_05_fgene-13-848879-g002.jpg
F2
was a 4-year-old boy also with typical features of RSTS (Figure 2E).
Pedigrees and schematic summary of genetic alteration discoveries in this study. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5. WT, wild type.
fgene-13-848879-g003.jpg
PMC9024331_05_fgene-13-848879-g003.jpg
F3
Unexpectedly, WES also failed to identify pathogenic variants within the CREBBP and EP300 loci (Figure 3E).
Chromatograms of confirmative PCR-based Sanger sequencing and segregation analysis results. (A) A de novo nonsense CREBBP mutation in case 2. (B) A de novo CREBBP 2-bp deletion in case 3. (C) The CREBBP nonsense mutation was detected in both case 4 and the proband's mother.
fgene-13-848879-g005.jpg
PMC9024331_04_fgene-13-848879-g005.jpg
F5
Further segregation analysis showed that the mutation had occurred de novo (Figure 5C).
PMC9024331_04
Clinical manifestations of the five RSTS cases. Positive findings of common RSTS characteristics, including distinctive facial features, and broadened thumbs and halluces, were noted in all of the enrolled cases. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5.
fgene-13-848879-g002.jpg
PMC9024331_05_fgene-13-848879-g002.jpg
F2
was a 4-year-old boy also with typical features of RSTS (Figure 2E).
Chromatograms of confirmative PCR-based Sanger sequencing and segregation analysis results. (A) A de novo nonsense CREBBP mutation in case 2. (B) A de novo CREBBP 2-bp deletion in case 3. (C) The CREBBP nonsense mutation was detected in both case 4 and the proband's mother.
fgene-13-848879-g005.jpg
PMC9024331_04_fgene-13-848879-g005.jpg
F5
Further segregation analysis showed that the mutation had occurred de novo (Figure 5C).
PMC9024331_05
Clinical manifestations of the five RSTS cases. Positive findings of common RSTS characteristics, including distinctive facial features, and broadened thumbs and halluces, were noted in all of the enrolled cases. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5.
fgene-13-848879-g002.jpg
PMC9024331_05_fgene-13-848879-g002.jpg
F2
was a 4-year-old boy also with typical features of RSTS (Figure 2E).
Pedigrees and schematic summary of genetic alteration discoveries in this study. (A) case 1. (B) case 2. (C) case 3. (D) case 4. (E) case 5. WT, wild type.
fgene-13-848879-g003.jpg
PMC9024331_05_fgene-13-848879-g003.jpg
F3
Unexpectedly, WES also failed to identify pathogenic variants within the CREBBP and EP300 loci (Figure 3E).