PMC9420874_01
Proband (arrow).
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F1
The proband had additional two affected family members (Figure 1).
Hand and facial features of the mother (A). Hand and facial features of the elder sister (B). Hand and facial features of the proband (C).
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F2
The three patients all had coarse craniofacial features including widely spaced downward-slanting palpebral fissures, low nasal bridge, blunt tip, broad nose, anteverted nares, and thick lips (Figure 2C). In addition, her elder sister had acne all over her face (Figure 2B), and her mother had a wide and open mouth, and thick lips with everted lower lip (Figure 2A).
X-rays of hands and spines. (A) Mother (B) Elder sister (C) Proband.
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F3
X-rays of spines showed that only the mother had scoliosis (Figure 3A).
Result of CNV-seq was seq (hg19) del (22) (q11.22-q11.23) (22997582-23637176) x 0.5. In the deletion region (marked with a red box), genes were colored by the pLI score.
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F4
CNV-seq showed that both the mother and the elder sister carried a CNVseq [hg19] del (22) (q11.22-q11.23) (22997582-23637176) x 0.5 (Figure 4).
Results of Sanger sequencing. (A) Father (B-D). Heterozygous RPS6KA3 gene variant (C) 898C>T (NM_004,586.3) in the mother, the elder sister, and the proband (the variant was marked with a red arrow).
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F5
WES identified a heterozygous nonsense RPS6KA3 gene variant c.898C>T (p.R300X), which was verified by Sanger sequencing (Figure 5).
Fold change was used for calculating mRNA relative expression. The levels of mRNA relative expression were significantly lower in the mother's and the elder sister's blood samples, and the levels of mRNA relative expression were significantly higher in the proband's blood sample.
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F6
The quantitative PCR (qPCR) data demonstrated that the levels of mRNA relative expression were significantly lower in the mother's and the elder sister's blood samples, and the levels of the mRNA relative expression were significantly higher in the proband's blood sample (Figure 6).