PMC10097981_01
(A,B) Fat, short and thick neck, dysplasia of the both auricles, low-set ears; (C) Cafe au lait spot on face, a bit broad nasal bridge and teeth sparse; (D,E) short hands and feet.
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F1
Spot on face, dysplasia and low-set ears, broad nasal bridge, strabismus, short and thick neck, and short upper limbs and fingers (Figure 1). She also showed deformation of the fingers, likely due to her actions of frequently biting or chewing on fingers.
Sanger sequencing results of the pedigree. The proband had a heterozygous variant of c.568C > T in ADNP gene.
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PMC10097981_01_fped-11-1122513-g002.jpg
F2
T, p.Gln190Ter) in exon 5 was discovered in the patient, which leads to premature termination of the gene coding process (Figures 3A,B). The variant was verified in the patient, but not found in other family members by Sanger sequencing (Figure 2).
(A,B) Illustrations denoting the mutant sites, (A), nucleotide sequence; (B), protein sequence; (C) evolutionary relationships of species; (D) amino acid conservation in mutant sites.
fped-11-1122513-g003.jpg
PMC10097981_01_fped-11-1122513-g003.jpg
F3
T, p.Gln190Ter) in exon 5 was discovered in the patient, which leads to premature termination of the gene coding process (Figures 3A,B). The variant was verified in the patient, but not found in other family members by Sanger sequencing (Figure 2). T (p.Gln190Ter) mutation is located in exon 5 of the ADNP gene and causes incorporation of a premature stop codon in the transcript, thereby truncating the protein (Figures 3A,B, 4). The variant c.568C > T was not found in gnomAD, EXAC, 1000genomes, or ESP6500. The conservative analysis indicated that the glutamate residue at position 190 was located in a highly evolutionary-conserved region (Figures 3C,D).
Illustrations denoting the mutant sites. Previously found varients in patients with HVDAS are depicted in black. The variants found in our patient p. Gln190* in red is the novel variant.
fped-11-1122513-g004.jpg
PMC10097981_01_fped-11-1122513-g004.jpg
F4
T (p.Gln190Ter) mutation is located in exon 5 of the ADNP gene and causes incorporation of a premature stop codon in the transcript, thereby truncating the protein (Figures 3A,B, 4). The variant c.568C > T was not found in gnomAD, EXAC, 1000genomes, or ESP6500.