Genetic and Phenotypic Spectrum of KMT2D Variants in Taiwanese Case Series of Kabuki Syndrome
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Group and Data Collection
2.2. Molecular Analysis
2.3. Study Limitations
2.4. Variant Classification
3. Results
3.1. Molecular Findings
3.2. Clinical Features
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 | Sex | KMT2D cDNA Change | KMT2D Amino Acid Change | Pathogenicity | ACMG Classification | Inheritance |
---|---|---|---|---|---|---|
1 | M | c.15461G>A | p.Arg5154Gln | Missense | Likely Pathogenic | De novo |
2 | M | c.10738C>T | p.Gln3580 * | Nonsense | Pathogenic | De novo |
3 | M | c.10378C>T | p.Gln3460 * | Nonsense | Pathogenic | De novo |
4 | M | c.11944C>T | p.Arg3982 * | Nonsense | Pathogenic | De novo |
5 | M | c.1113-40_1152del80insTA | - | Insertion/ Deletion | Likely Pathogenic | Unknown |
6 | F | c.15953_56delTATT | p.Leu5318Serfs *14 | Frameshift | Pathogenic | De novo |
7 | F | c.13040_13041delAG | p.Gln4347Argfs *24 | Frameshift | Pathogenic | De novo |
c.7144C>T | p.Pro2382Ser | Missense | Uncertain Significance | Unknown | ||
8 | M | c.10741-7A>G | - | Splicing | Likely Pathogenic | Unknown |
c.15802_15804delATT | p.Ile5268del | Deletion | Pathogenic | De novo | ||
9 | F | c.7205C>A | p.Ser2402 * | Nonsense | Pathogenic | De novo |
10 | F | c.15802_15804delATT | p.Ile5268del | Deletion | Pathogenic | De novo |
11 | M | c.7205C>A | p.Ser2402 * | Nonsense | Pathogenic | De novo |
12 | F | c.15953_56delTATT | p.Leu5318Serfs *14 | Frameshift | Pathogenic | De novo |
13 | M | c.15461G>A | p.Arg5154Gln | Missense | Likely Pathogenic | De novo |
14 | M | c.11149C>T | p.Gln3717 * | Nonsense | Likely Pathogenic | De novo |
15 | F | c.7144C>T | p.Pro2382Ser | Missense | Uncertain Significance | Unknown |
16 | F | c.7144C>T | p.Pro2382Ser | Missense | Uncertain Significance | Unknown |
c.16412+16delG | - | Deletion | Likely Pathogenic | Unknown | ||
17 | F | c.15461G>A | p.Arg5154Gln | Missense | Likely Pathogenic | De novo |
18 | M | c.8938delG | p.Ala2980Profs *24 | Frameshift | Pathogenic | De novo |
19 | M | c.11170C>T | p.Pro2382Ser | Missense | Uncertain Significance | Unknown |
c.16412+16delG | - | Deletion | Likely Pathogenic | Unknown | ||
20 | F | c.8938delG | p.Ala2980Profs *24 | Frameshift | Pathogenic | De novo |
21 | F | c.15461G>A | p.Arg5154Gln | Missense | Likely Pathogenic | De novo |
22 | F | c.16412+16delG | - | Deletion | Likely Pathogenic | Unknown |
23 | M | c.10741-7A>G | - | Splicing | Likely Pathogenic | Unknown |
Clinical Feature | Number of Patients (Total = 23) | Percentage (%) |
---|---|---|
Distinct facial features | 23 | 100 |
Intellectual disability | 23 | 100 |
Developmental delay | 22 | 95.7 |
Speech delay | 18 | 78.3 |
Hypotonia | 16 | 69.6 |
Congenital heart defects | 16 | 69.6 |
ASD, ostium secundum | 6/16 | 37.5 |
VSD, perimembranous subaortic | 3/16 | 18.8 |
Aortic coarctation | 3/16 | 18.8 |
Bicuspid aortic valve | 2/16 | 12.5 |
Persistent left superior vena cava | 2/16 | 12.5 |
Mitral valve prolapse | 2/16 | 12.5 |
Mitral regurgitation | 2/16 | 12.5 |
Patent ductus arteriosus | 2/16 | 12.5 |
Mitral stenosis | 1/16 | 6.3 |
Aberrant right subclavian artery | 1/16 | 6.3 |
Vascular ring | 1/16 | 6.3 |
Dilated aortic root | 1/16 | 6.3 |
Interrupted aortic arch | 1/16 | 6.3 |
Subaortic ridge | 1/16 | 6.3 |
Left isomerism of the heart | 1/16 | 6.3 |
Aortic dissection | 1/16 | 6.3 |
Redundant mitral valve | 1/16 | 6.3 |
Redundant tricuspid valve | 1/16 | 6.3 |
Recurrent infections | 15 | 65.2 |
Short stature | 14 | 60.9 |
Feeding difficulties | 10 | 43.5 |
Hearing impairment | 9 | 39.1 |
Seizures | 6 | 26.1 |
Cleft palate | 6 | 26.1 |
Renal anomalies | 5 | 21.7 |
Preauricular pits | 4 | 17.4 |
Ophthalmologic abnormalities | 4 | 17.4 |
Sacral dimple | 2 | 8.7 |
Cryptorchidism | 1 | 4.3 |
Hip dislocation | 1 | 4.3 |
Premature thelarche | 1 | 4.3 |
Gastrointestinal anomalies | 1 | 4.3 |
Dental anomalies | 1 | 4.3 |
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Lee, C.-L.; Chuang, C.-K.; Chen, M.-R.; Lin, J.-L.; Chiu, H.-C.; Chang, Y.-H.; Tu, Y.-R.; Lo, Y.-T.; Lin, H.-Y.; Lin, S.-P. Genetic and Phenotypic Spectrum of KMT2D Variants in Taiwanese Case Series of Kabuki Syndrome. Diagnostics 2024, 14, 1815. https://doi.org/10.3390/diagnostics14161815
Lee C-L, Chuang C-K, Chen M-R, Lin J-L, Chiu H-C, Chang Y-H, Tu Y-R, Lo Y-T, Lin H-Y, Lin S-P. Genetic and Phenotypic Spectrum of KMT2D Variants in Taiwanese Case Series of Kabuki Syndrome. Diagnostics. 2024; 14(16):1815. https://doi.org/10.3390/diagnostics14161815
Chicago/Turabian StyleLee, Chung-Lin, Chih-Kuang Chuang, Ming-Ren Chen, Ju-Li Lin, Huei-Ching Chiu, Ya-Hui Chang, Yuan-Rong Tu, Yun-Ting Lo, Hsiang-Yu Lin, and Shuan-Pei Lin. 2024. "Genetic and Phenotypic Spectrum of KMT2D Variants in Taiwanese Case Series of Kabuki Syndrome" Diagnostics 14, no. 16: 1815. https://doi.org/10.3390/diagnostics14161815