Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Subjects
2.2. DNA Extraction and Quantification
2.3. Library Construction and Exome Sequencing
2.4. Data Processing
2.5. Variant Filtration Steps
2.6. Primer Design and Variant Confirmation
2.7. Homology Protein Modeling
2.7.1. NDST1 (p.Asp656Asn)
2.7.2. METTL23 (p.Phe104Leu)
3. Results
3.1. Clinical Manifestations
3.1.1. Family A
3.1.2. Family B
3.2. Molecular Evaluation
3.3. Homology Modeling
3.3.1. NDST1 (p.Asp656Asn)
3.3.2. METTL23 (p.Phe104Leu)
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinical Findings | Family A | Family B | |||
---|---|---|---|---|---|
Sex | M | F | F | F | F |
Age (years) | 12 | 10 | 24 | 12 | 10 |
Developmental delay | + | + | + | + | + |
Intellectual disability | ++ | ++ | ++ | ++ | + |
Microcephaly | - | - | - | - | - |
Hypothyroidism | - | - | - | - | - |
Speech development delay | + | + | - | - | - |
Learning disability | + | + | + | + | + |
Behavioral abnormalities | + | + | + | + | + |
Dysmorphic features | - | - | + | + | - |
Skeletal problem | - | - | - | - | - |
Ophthalmic problem | - | - | - | - | - |
Skin problem | - | - | - | - | - |
Seizures | + | + | + | + | + |
Social activity | + | + | + | + | - |
Muscular dystrophy | - | - | - | - | - |
Self biting | - | - | ++ | ++ | + |
Family ID | Family A | Family B |
---|---|---|
Affected individuals | IV-1, IV-2 | V-2, V-4, V-5 |
Transcript ID | NM_001543.5 | NM_001206984.3 |
Gene name | NDST1 | METTL23 |
MIM number | 616116 | 615942 |
Chromosome position | Chr5:149922529 | Chr17:74729285 |
Nucleotide change | c.1966G>A | c.310T>C |
Protein change | p.Asp656Asn | p.Phe104Leu |
SNP number | rs150320391 | - |
GnomAD frequency | 0.000016 | - |
SIFT score | 0.08/T | 0/D |
Polyphen2 score | 0.992/D | 0.891/PD |
Mutation taster score | 1/D | 1/D |
CADD score | 27.4 | 31 |
PROVEAN score | −0.17/N | −4.67/D |
ACMG classification | PM1 | PM2 |
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Share and Cite
Khan, A.; Miao, Z.; Umair, M.; Ullah, A.; Alshabeeb, M.A.; Bilal, M.; Ahmad, F.; Rappold, G.A.; Ansar, M.; Carapito, R. Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants. Genes 2020, 11, 1021. https://doi.org/10.3390/genes11091021
Khan A, Miao Z, Umair M, Ullah A, Alshabeeb MA, Bilal M, Ahmad F, Rappold GA, Ansar M, Carapito R. Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants. Genes. 2020; 11(9):1021. https://doi.org/10.3390/genes11091021
Chicago/Turabian StyleKhan, Amjad, Zhichao Miao, Muhammad Umair, Amir Ullah, Mohammad A. Alshabeeb, Muhammad Bilal, Farooq Ahmad, Gudrun A. Rappold, Muhammad Ansar, and Raphael Carapito. 2020. "Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants" Genes 11, no. 9: 1021. https://doi.org/10.3390/genes11091021