PMC9388729_01
Identification of a de novo splicing variant in a patient with global developmental delay, mild intellectual disability and speech delay, and autistic features.(A,B) Pedigree diagram and DNA sequencing results of the family. A heterozygous de novo splicing variant in FOXP1 (NM_032682: c.1652 + 5 G>A) was present in the proband (indicated by an arrow). This variant was not found in his parents and sister, who were asymptomatic. The orange box indicates the variant site. (C) Sequence electropherograms of FOXP1 obtained from cDNA from the patient revealed that c.1652 + 5 G>A causes the skipping of exon 18 in mutant (MT) clones as compared to wild-type (WT) ones. (D) Schematic diagrams of WT and MT FOXP1. The exon 17, 18, and 19 sequences are represented in upper cases framed by blue, orange, and green boxes, respectively. The splicing variant (designated in red) resulted in the skipping of exon 18 and a new premature stop codon at 511 (p.Asn511*).
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F1
He had one older unaffected sister and there was no family history of the disease (Figure 1A). It was neither detected in the samples of his parents nor his sister, indicating that the inheritance status was de novo (Figure 1B). TA cloning followed by sequencing further revealed that the splice-site variant caused the skipping of exon 18 (122 bp) and presumably created a premature stop codon at position 511 (p.Asn511*) (Figures 1C,D).