PMC8155672_01
Clinical images of the proband. (A) The facial characteristics of the proband (broad forehead, high anterior hairline, and a thin upper vermilion). (B) Spastic gait and dystonia of wrists. (C) Contracture of the fingers. (D) Scarring and pigmentation following ulceration of the leg. (E) Deformities of the interphalangeal joints and ulnar deviation of the left metacarpal. (F) Deformity of both maxilla and mandible. (G) Complete loss of teeth and alveolar bone. (H) Multiple intracranial calcifications (bilateral lenticular and frontal lobe).
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F1
He had a broad forehead, a high anterior hairline, and a thin upper vermilion (Figure 1A). Neurological examination revealed dystonia of the wrist, a sluggish pharyngeal reflex, and spastic paraplegia of both lower limbs (Figure 1B). X-ray confirmed deformities of the interphalangeal joints of both hands and ulnar deviation of the left metacarpal (Figure 1E). Skull X-rays showed a complete loss of teeth and alveolar jaw bone (Figure 1F). Deformities of the maxilla and mandible were also observed (Figure 1G). Multiple intracranial calcifications were evident on cranial computed tomography (CT) imaging (Figure 1H).
PMC8155672_02
Clinical images of the proband. (A) The facial characteristics of the proband (broad forehead, high anterior hairline, and a thin upper vermilion). (B) Spastic gait and dystonia of wrists. (C) Contracture of the fingers. (D) Scarring and pigmentation following ulceration of the leg. (E) Deformities of the interphalangeal joints and ulnar deviation of the left metacarpal. (F) Deformity of both maxilla and mandible. (G) Complete loss of teeth and alveolar bone. (H) Multiple intracranial calcifications (bilateral lenticular and frontal lobe).
fgene-12-660953-g0001.jpg
PMC8155672_02_fgene-12-660953-g0001.jpg
F1
He had a broad forehead, a high anterior hairline, and a thin upper vermilion (Figure 1A). Neurological examination revealed dystonia of the wrist, a sluggish pharyngeal reflex, and spastic paraplegia of both lower limbs (Figure 1B). X-ray confirmed deformities of the interphalangeal joints of both hands and ulnar deviation of the left metacarpal (Figure 1E). Skull X-rays showed a complete loss of teeth and alveolar jaw bone (Figure 1F). Deformities of the maxilla and mandible were also observed (Figure 1G). Multiple intracranial calcifications were evident on cranial computed tomography (CT) imaging (Figure 1H).
Molecular findings. (A) Family tree. (B) A de novo IFIH1 mutation c.1465G > T (p.Ala489Ser) confirmed by Sanger sequencing. (C) Quantitative analysis of interferon-stimulated genes. The expression of interferon-stimulated genes (IFI27, IFIT1, IFI44L, ISG15, SIGLEC1, and RSAD2) was analyzed by quantitative PCR. The relative expression of each interferon-stimulated gene in PBMCs (peripheral blood mononuclear cells) isolated from the patient was normalized to controls and represented as a mean and standard deviation. Control PBMCs were donated from a healthy individual who had been age- and gender-matched. All experiments were carried out in triplicate.
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F2
T (p.Ala489Ser)] but no other disease-causing genes were detected (Figure 2A). Further Sanger sequencing showed that the parents of the proband did not possess this mutation, indicating that this was a de novo mutation (Figure 2B). The proband showed higher interferon-stimulated global gene expression than a healthy control (matched with age and gender) (Figure 2C).