Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family
Abstract
:1. Introduction
2. Case Presentation
2.1. Patients
2.2. Whole Exome Sequencing, Variant Calling and Annotation
2.3. Filtration of Variants
2.4. Sanger Sequencing for Variant Confirmation and Familial Segregation Analysis
2.5. In Silico Analyses and Pathogenic Interpretation
2.6. Amino Acid Sequence Alignment and Protein Analyses
3. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Patients | P1 | P2 |
---|---|---|
Gender | Male | Female |
Age of first admission | 6-year-old | 4-year-old |
CK (UI/L) (Normal range: 24–229) | 942 | 523 |
AST (UI/L) (Normal range: 15–55) | 33.9 | 40.3 |
ALT (UI/L) (Normal range: 5–40) | 10.1 | 32.7 |
Head and Neck | Myopathic face Open mouth Prominent jaw Bifid uvula | Myopathic face Open mouth Prominent jaw Broad uvula |
Skeletal system | Hyperlordosis A wide-based stance Distal contractures of the fingers | Hyperlordosis A wide-based gait absent reflexes Distal contractures of the fingers |
Musculature | Muscular atrophy Macroglossia Motor delay Positive Gowers sign No pseudohypertrophy of tongue and calf muscles Independent walking at 5 years of age Toe walking from 6 years of age Inability to walk from 9 years of age | Muscular atrophy Macroglossia Motor delay Positive Gowers sign No pseudohypertrophy of tongue and calf muscles Independent walking at 4 years of age Toe walking from 5 years of age |
Growth development | Delay Normal verbal cognition | Delay Normal verbal cognition |
Nervous system | Diffuse white matter changes: hyperintense on T2W and FLAIR sequences, hypointense on T1W sequence Not restricted on diffusion with symmetric appearance Normal corpus callosum, ventricular, pontocerebellar angle, cerebral nerves, medulla, pons and high cervical spinal cord. No fluid collection in meningeal space. No history of seizure | Diffuse white matter changes: hyperintense on T2W and FLAIR sequences, hypointense on T1W sequence Not restricted on diffusion with symmetric appearance Normal corpus callosum, ventricular, pontocerebellar angle, cerebral nerves, medulla, pons and high cervical spinal cord. No fluid collection in meningeal space. No history of seizure |
Heart ultrasound | Normal | Normal |
Respiratory system | Normal | Normal |
Digestive system | Normal | Normal |
Karyotype | 46, XY | 46, XX |
Screening pathogenic variants in the SMN and GAA genes | Negative | Negative |
Variant | c.778C>T (p.H260Y) | c.2987G>A (p.C996Y) |
---|---|---|
Prediction (Score) | Prediction (Score) | |
Align-GVGD | Pathogenic (C65) | Pathogenic (C65) |
CADD (Phred-scaled score) | Likely deleterious (24.1) | Likely deleterious (29.7) |
Fathmm | Tolerated (1.41) | Damaging (−3.40) |
Mutation Taster | Disease causing (1) | Disease causing (1) |
Mutation Assessor | Low impact (0.9) | High impact (4.14) |
MutPred | Pathogenicity (0.822) | Pathogenicity (0.985) |
PANTHER | Possibly damaging (361) | Probably damaging (1036) |
PhD-SNP | Neutral (RI 6) | Disease (RI 7) |
PON-P2 | Unknown (0.272) | Pathogenic (0.973) |
PolyPhen-2 | Damaging (0.988) | Damaging (0.998) |
PROVEAN | Deleterious (−3.247) | Deleterious (−10.385) |
SIFT | Tolerated (0.148) | Damaging (0) |
SNP&GO | Neutral (RI 5) | Disease (RI 9) |
SNAP | Neutral (−32) | Effect (53) |
UMD-Predictor | Pathogenic (78) | Pathogenic (100) |
ACMG classification | Likely pathogenic (PM2, PP1–PP4) | Likely pathogenic (PM2, PM5, PP1–PP4) |
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Nguyen, N.-L.; Ngoc, C.T.B.; Vu, C.D.; Nguyen, T.T.H.; Nguyen, H.H. Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family. Diagnostics 2020, 10, 741. https://doi.org/10.3390/diagnostics10100741
Nguyen N-L, Ngoc CTB, Vu CD, Nguyen TTH, Nguyen HH. Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family. Diagnostics. 2020; 10(10):741. https://doi.org/10.3390/diagnostics10100741
Chicago/Turabian StyleNguyen, Ngoc-Lan, Can Thi Bich Ngoc, Chi Dung Vu, Thi Thu Huong Nguyen, and Huy Hoang Nguyen. 2020. "Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family" Diagnostics 10, no. 10: 741. https://doi.org/10.3390/diagnostics10100741