Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient | Age * | Family | Relative | Genomic Coordinate (hg19) | Variant | Exon/ Intron | Variant Type | Inheritance | Allele Frequency † | Pathogenicity Predictors ‡ | CADD | ACMG Prediction § | Detection Method | Reference |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OGS1360 | 13 | 1 | Pr | chr11:2906484 | CDKN1C(NM_000076.2):c.236G>C,p.(Trp79Ser) | 1 | missense | maternal | - | 24/26 | 28.39 | VUS | SS | This study |
OGS1810 | 10 | 1 | S | chr11:2906484 | CDKN1C(NM_000076.2):c.236G>C,p.(Trp79Ser) | 1 | missense | maternal | - | 24/26 | 28.39 | VUS | SS | This study |
OGS1380 | 12 | 2 | Pr | chr11:2906527 | CDKN1C(NM_000076.2):c.193T>C,p.(Phe65Leu) | 1 | missense | maternal | - | 23/26 | 28.5 | VUS | SS | This study |
OGS1774 | 9 | 2 | B | chr11:2906527 | CDKN1C(NM_000076.2):c.193T>C,p.(Phe65Leu) | 1 | missense | maternal | - | 23/26 | 28.5 | VUS | SS | This study |
OGS1449 | 12 | 3 | Pr | chr11:2906512 | CDKN1C(NM_000076.2):c.208C>A,p.(Pro70Thr) | 1 | missense | maternal | - | 24/26 | 25.6 | VUS | SS | This study |
OGS1584 | 20 | 4 | S | chr11:2905379 | CDKN1C(NM_000076.2):c.821-15C>A | intron 1 | Non-coding | maternal | - | 1/2 | 19.38 | VUS | SS | This study |
OGS1775 | 16 | 4 | Pr | chr11:2905379 | CDKN1C(NM_000076.2):c.821-15C>A | intron 1 | Non-coding | maternal | - | 1/2 | 19.38 | VUS | SS | This study |
OGS2051 | 18 | 5 | Pr | chr11:2906483 | CDKN1C(NM_000076.2):c.237G>A,p.(Trp79Ter) | 1 | nonsense | maternal | - | 8/9 | 37 | P | SS | This study |
OGS2052 | 12 | 6 | Pr | chr11:2906482 | CDKN1C(NM_000076.2):c.238A>C,p.(Thr80Pro) | 1 | missense | maternal | - | ago-26 | 23.7 | VUS | GP | This study |
OGS2166 | 17 | 6 | S | chr11:2906482 | CDKN1C(NM_000076.2):c.238A>C,p.(Thr80Pro) | 1 | missense | maternal | - | 8/26 | 23.7 | VUS | GP | This study |
OGS1492 | 32 | 7 | Pr | chr11:2906141 | CDKN1C(NM_000076.2):c.579del,p.(Pro194GlnfsTer78) | 1 | frameshift | maternal | - | - | - | LP | SS | [24] |
OGS1493 | 23 | 7 | B | chr11:2906141 | CDKN1C(NM_000076.2):c.579del,p.(Pro194GlnfsTer78) | 1 | frameshift | maternal | - | - | - | LP | SS | [24] |
OGS1494 | 28 | 7 | S | chr11:2906141 | CDKN1C(NM_000076.2):c.579del,p.(Pro194GlnfsTer78) | 1 | frameshift | maternal | - | - | - | LP | SS | [24] |
OGS1074 | 14 | 8 | Pr | chr11:2906709 | CDKN1C(NM_000076.2):c.11C>T,p.(Ala4Val) | 1 | missense | maternal | 1/36.514 | 5/24 | 14.67 | VUS | GP | [23] |
OGS542 | 16 | 9 | Pr | chr11:2906622 | CDKN1C(NM_000076.2):c.98T>A,p.(Leu33His) | 1 | missense | maternal | - | 8/10 | 26.4 | VUS | SS | [23] |
OGS4 | 24 | 10 | Pr | chr11:2906488 | CDKN1C(NM_000076.2):c.232C>T,p.(Gln78Ter) | 1 | nonsense | de novo | - | 7/9 | 36 | P | SS | [23] |
OGS851 | 15 | 11 | Pr | chr11:2906026 | CDKN1C(NM_000076.2):c.694C>T,p.(Gln232Ter) | 1 | nonsense | maternal | - | 5/9 | 37 | LP | SS | [23] |
OGS145 | 19 | 12 | Pr | chr11:2905366 | CDKN1C(NM_000076.2):c.821-2A>G | intron 1 | splicing | maternal | - | 7/9 | 33 | P | SS | [23] |
OGS1234 | 14 | 13 | Pr | chr11:2905340 | CDKN1C(NM_000076.2):c.845delC,p.(Ser282Ter) | 2 | nonsense | maternal | - | - | - | LP | SS | [23] |
OGS491 | 20 | 14 | Pr | chr11:2905340 | CDKN1C(NM_000076.2):c.845C>A,p.(Ser282Ter) | 2 | nonsense | maternal | - | 7/23 | 37 | P | SS | [23] |
OGS1356 | 45 | 15 | Pr | chr11:2905340 | CDKN1C(NM_000076.2):c.845C>G,p.(Ser282Ter) | 2 | nonsense | N/E | - | 7/23 | 36 | LP | SS | [23] |
Clinical Features | No. Patients | % Patients | ||
---|---|---|---|---|
Macroglossia | HP:0000158 | 21 | 100.0 | |
Omphalocele | HP:0001539 | 13 | 61.9 | |
Posterior helix pits | HP0008523 | 8 | 38.1 | |
Anterior earlobe creases | HP:0009908 | 8 | 38.1 | |
Transient hypoglycaemia | HP:0001998 | 8 | 38.1 | |
Cleft palate | HP:0000175 | 7 | 33.3 | |
Overgrowth | HP:0001548 | 7 | 33.3 | |
Premature birth | HP:0001622 | 6 | 28.6 | (ranging from 29 to 36 weeks) |
Umbilical hernia | HP:0001537 | 5 | 23.8 | |
Nevus flammeus | HP:0001052 | 5 | 23.8 | |
Inguinal hernia | HP:0000023 | 4 | 19.0 | |
Hemihypertrophy | HP:0001528 | 3 | 14.3 | |
Thin upper lip vermilion | HP:0000219 | 3 | 14.3 | |
Coarse facial features | HP:0000280 | 3 | 14.3 | |
Anterior open-bite malocclusion | HP:0009102 | 3 | 14.3 | |
Capillary malformation | HP:0025104 | 2 | 9.5 | |
Hepatomegaly | HP:0002240 | 2 | 9.5 | |
Postaxial foot polydactyly | HP:0001830 | 2 | 9.5 | |
Premature tooth eruption | HP:0006288 | 2 | 9.5 | |
Sensorineural hearing impairment | HP:0000407 | 2 | 9.5 | |
Supernumerary flexion creases of the fingers | HP:0040064 | 2 | 9.5 | |
Neoplasm (ganglioneuroma) | HP:0002664 | 1 | 4.8 | |
Macrocephaly, craniosynostosis, hypotonia, cryptorchidism, hypospadias, thyroglossal cyst, renal cyst, nephromegaly, splenomegaly, haemangioma, prominent upper eyelids, strabismus, apnoea, psoriasiform dermatitis, visceromegaly | 1 | 4.8 |
Clinical Features | Patients and Consensus BWSp Scoring * | ||||||||||||
OGS1360 | OGS1810 | OGS1380 | OGS1774 | OGS1449 | OGS1584 | OGS1775 | OGS2051 | OGS2052 | OGS2166 | ||||
Score 5 | Score 5 | Score 4 | Score 3 | Score 4 | Score 8 | Score 5 | Score 6 | Score 5 | Score 5 | ||||
Macroglossia | HP:0000158 | CF | X | X | X | X | X | X | X | X | X | X | |
Omphalocele | HP:0001539 | CF | X | X | X | X | |||||||
Anterior earlobe creases | HP:0009908 | CF | X | X | X | ||||||||
Overgrowth | HP:0001548 | SF | X | X | X | X | |||||||
Posterior helix pits | HP0008523 | SF | X | X | |||||||||
Transient hypoglycaemia | HP:0001998 | SF | X | X | X | X | |||||||
Umbilical hernia | HP:0001537 | SF | X | X | |||||||||
Nevus flammeus | HP:0001052 | SF | X | X | X | ||||||||
Hemihypertrophy | HP:0001528 | SF | X | X | |||||||||
Hepatomegaly | HP:0002240 | SF | |||||||||||
Nephromegaly | HP:0000105 | SF | |||||||||||
Clinical Features | Patients and Consensus BWSp Scoring * | ||||||||||||
OGS1492 | OGS1493 | OGS1494 | OGS1074 | OGS542 | OGS4 | OGS851 | OGS145 | OGS1234 | OGS491 | OGS1356 | |||
Score 5 | Score 5 | Score 5 | Score 5 | Score 11 | Score 6 | Score 6 | Score 4 | Score 6 | Score 6 | Score 6 | |||
Macroglossia | HP:0000158 | CF | X | X | X | X | X | X | X | X | X | X | X |
Omphalocele | HP:0001539 | CF | X | X | X | X | X | X | X | X | X | ||
Anterior earlobe creases | HP:0009908 | CF | X | X | X | X | X | ||||||
Overgrowth | HP:0001548 | SF | X | X | X | X | |||||||
Posterior helix pits | HP0008523 | SF | X | X | X | X | X | X | |||||
Transient hypoglycaemia | HP:0001998 | SF | X | X | X | X | |||||||
Umbilical hernia | HP:0001537 | SF | X | X | X | ||||||||
Nevus flammeus | HP:0001052 | SF | X | X | |||||||||
Hemihypertrophy | HP:0001528 | SF | X | ||||||||||
Hepatomegaly | HP:0002240 | SF | X | X | |||||||||
Nephromegaly | HP:0000105 | SF | X |
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Cardoso, L.C.d.A.; Parra, A.; Gil, C.R.; Arias, P.; Gallego, N.; Romanelli, V.; Kantaputra, P.N.; Lima, L.; Llerena Júnior, J.C.; Arberas, C.; et al. Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants. Cancers 2022, 14, 3807. https://doi.org/10.3390/cancers14153807
Cardoso LCdA, Parra A, Gil CR, Arias P, Gallego N, Romanelli V, Kantaputra PN, Lima L, Llerena Júnior JC, Arberas C, et al. Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants. Cancers. 2022; 14(15):3807. https://doi.org/10.3390/cancers14153807
Chicago/Turabian StyleCardoso, Leila Cabral de Almeida, Alejandro Parra, Cristina Ríos Gil, Pedro Arias, Natalia Gallego, Valeria Romanelli, Piranit Nik Kantaputra, Leonardo Lima, Juan Clinton Llerena Júnior, Claudia Arberas, and et al. 2022. "Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants" Cancers 14, no. 15: 3807. https://doi.org/10.3390/cancers14153807
APA StyleCardoso, L. C. d. A., Parra, A., Gil, C. R., Arias, P., Gallego, N., Romanelli, V., Kantaputra, P. N., Lima, L., Llerena Júnior, J. C., Arberas, C., Guillén-Navarro, E., Nevado, J., Spanish OverGrowth Registry Initiative, Tenorio-Castano, J., & Lapunzina, P. (2022). Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants. Cancers, 14(15), 3807. https://doi.org/10.3390/cancers14153807