The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies
Abstract
:1. Introduction
2. Materials and Methods
2.1. DNA Methylation Profiling Analysis
2.2. WGS Analysis
2.3. Structural Analysis
3. Results
3.1. Clinical Findings
3.2. Molecular Findings and Structural Analysis
3.3. Assessment of the Clinical Profile Associated with Arg99Gln
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Present Study | Individual 11 [11] | |
---|---|---|
Sex | Female | Female |
Age at evaluation | 14 years | 4 years 5 months |
HNRNPC variant | c.296G>A, p.Arg99Gln (de novo) | c.296G>A, p.Arg99Gln (de novo) |
ACMG variant classification | PS2, PM2 (likely pathogenic) | PS2, PM2 (likely pathogenic) |
Molecular analysis | WGS (trio) | WGS (trio) |
Other clinically relevant variants | None | None |
Phenotypic information | ||
Pregnancy and birth | Normal | Normal, urinary tract infection |
Gestational age (weeks) | 40 | 40 + 4 |
Weight at birth (g) | 3730 | 3540 |
Length at birth (cm) | 51 | |
OFC at birth (cm) | 36 | 33 |
Apgar score | 8–9 | |
Growth parameters | 18 years | 6 years, 8 months |
Height (cm) | 142.3 cm (−3.0 SD); | 122.9 cm (0.7 SD) |
Weight (kg) | 40.9 kg (−1.8 SD); | 29.5 kg (1.7 SD) |
OFC (cm) | 50 cm (−3.0 SD) | 4y5m: 49.3 cm (−1.7 SD) |
First words | No words | 3 years |
Walking | 2.5 years | 2 years |
Language development | No words | Few single words and signs |
Gross motor skills | Mild delay | Mild delay |
Cognitive deficit | Moderate (IQ 42) | Mild |
Seizures | No | No |
Hypo-/hypertonia | No | No |
Movement disorder | No | No |
MRI anomalies | Aplasia of left cochlea and hypoplasia of the right cochlea | Absent cochlea (right), hypoplasia of the left cochlea, absent cochlear nerves |
Behavioral anomalies | Stress-related hetero-aggressiveness, stereotypies | None |
Sleeping problems | No | No |
Facial dysmorphism | Broad and slightly receding forehead, high upper hairline, thick eyebrows, mild synophrys, wave-shaped lids, mild eversion of lower lateral eyelids, narrow and upslanted palpebral fissures, mildly deep-set eyes, deep and long philtrum, sharp nose, anteverted nares, thin upper lip, prominent malar region, preauricular fistula | Broad and slightly receding forehead, high upper hairline, mildly thick eyebrows, mild synophrys, wave-shaped lids, everted lower lateral eyelids, mildly upslanted palpebral fissures, deep-set eyes, smooth and long philtrum, anteverted nares, thin upper lip, prominent malar region, notched lower lateral incisor |
Eyes/vision | Bilateral colobomatous microphthalmia | Bilateral colobomatous microphthalmia |
Hearing | Sensorineural hearing loss | Sensorineural hearing loss |
Cardiac problems | Patent ductus arteriosus | |
Renal problems | None | None |
Endocrinological problems | Delayed menarche, growth delay, pituitary gland hypoplasia | Premature thelarche |
Additional features | Short and broad distal phalanx of the first finger of the hands, hirsutism | Prominent finger pads, hirsute legs, single gray scalp hair |
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Chiriatti, L.; Priolo, M.; Onesimo, R.; Carvetta, M.; Leoni, C.; Bruselles, A.; Radio, F.C.; Cappelletti, C.; Ferilli, M.; Ricci, D.; et al. The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies. Genes 2025, 16, 176. https://doi.org/10.3390/genes16020176
Chiriatti L, Priolo M, Onesimo R, Carvetta M, Leoni C, Bruselles A, Radio FC, Cappelletti C, Ferilli M, Ricci D, et al. The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies. Genes. 2025; 16(2):176. https://doi.org/10.3390/genes16020176
Chicago/Turabian StyleChiriatti, Luigi, Manuela Priolo, Roberta Onesimo, Mattia Carvetta, Chiara Leoni, Alessandro Bruselles, Francesca Clementina Radio, Camilla Cappelletti, Marco Ferilli, Daniela Ricci, and et al. 2025. "The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies" Genes 16, no. 2: 176. https://doi.org/10.3390/genes16020176
APA StyleChiriatti, L., Priolo, M., Onesimo, R., Carvetta, M., Leoni, C., Bruselles, A., Radio, F. C., Cappelletti, C., Ferilli, M., Ricci, D., Niceta, M., Cordeddu, V., Ciolfi, A., Mancini, C., Zampino, G., & Tartaglia, M. (2025). The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies. Genes, 16(2), 176. https://doi.org/10.3390/genes16020176