Biallelic Loss-of-Function Variant in MINPP1 Causes Pontocerebellar Hypoplasia with Characteristic Severe Neurodevelopmental Disorder
Abstract
1. Introduction
2. Results
2.1. Clinical Description
2.2. Neuroradiological Findings
2.3. Molecular Findings
2.4. Untargeted Metabolomics
3. Discussion
4. Materials and Methods
4.1. Ethical Approval
4.2. Genome Sequencing and Variant Prioritization
4.3. Untargeted Metabolomics Sample Preparation and Analysis
4.4. Cell Culture
4.5. Gene Expression and Western Blot Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PCH | Pontocerebellar hypoplasia |
MINPP1 | Multiple Inositol Polyphosphate Phosphatase 1 |
PCs | Phosphatidylcholines |
PBMCs | Peripheral blood mononuclear cells |
ATCs | Activated T cells |
HD | Healthy donor |
CT | Threshold cycle |
EBV-B | Epstein–Barr virus-immortalized B cells |
FC | Fold change |
RT-qPCR | Real-time quantitative polymerase chain reaction |
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Number of Affected | Position (GRCh37\hg19) | HGVS cDNA | HGVS Protein | Exon | Zygosity | |
---|---|---|---|---|---|---|
Present report | 1 | chr10:89312171 | c.1401del | p.Ser468Valfs*10 | 5 | Homozygous |
Appelhof et al. [7] | 2 | chr10:89264735 | c.75_94del | p.Leu27Argfs*39 | 1 | Homozygous |
2 | chr10:89272896 | c.851C>A | p.Ala284Asp | 3 | Homozygous | |
1 | chr10:89311981 | c.1210C>T | p.(Arg404*) | 5 | Homozygous | |
3 | chr10:89280851 | c.992T>G | p.(Ile331Ser) | 4 | Homozygous | |
Ucuncu et al. [6] | 2 | chr10:89264893 | c.223_224insGGGGG | p.Glu75Glyfs*30 | 1 | Homozygous |
1 | chr10:89264829 chr10:89264971 | c.157T>G c.300del | p.Tyr53Asp p.Lys101Serfs*2 | 1 1 | Compound Heterozygous | |
1 | chr10:89311973 | c.1202G>A | p.Arg401Gln | 5 | Homozygous | |
1 | chr10:89312227 | c.1456G>A | p.Glu486Lys | 5 | Homozygous | |
1 | chr10:89264853 | c.181_182insGAC | p.Leu61* | 1 | Homozygous | |
2 | chr10:89268137 | c.682T>C | p.Phe228Leu | 2 | Homozygous |
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Al-Maraghi, A.; Shaath, R.; Ford, K.; Aamer, W.; AlRayahi, J.; Hussein, S.; Aliyev, E.; Agrebi, N.; Kohailan, M.; Hubrack, S.Z.; et al. Biallelic Loss-of-Function Variant in MINPP1 Causes Pontocerebellar Hypoplasia with Characteristic Severe Neurodevelopmental Disorder. Int. J. Mol. Sci. 2025, 26, 5213. https://doi.org/10.3390/ijms26115213
Al-Maraghi A, Shaath R, Ford K, Aamer W, AlRayahi J, Hussein S, Aliyev E, Agrebi N, Kohailan M, Hubrack SZ, et al. Biallelic Loss-of-Function Variant in MINPP1 Causes Pontocerebellar Hypoplasia with Characteristic Severe Neurodevelopmental Disorder. International Journal of Molecular Sciences. 2025; 26(11):5213. https://doi.org/10.3390/ijms26115213
Chicago/Turabian StyleAl-Maraghi, Aljazi, Rulan Shaath, Katherine Ford, Waleed Aamer, Jehan AlRayahi, Sura Hussein, Elbay Aliyev, Nourhen Agrebi, Muhammad Kohailan, Satanay Z. Hubrack, and et al. 2025. "Biallelic Loss-of-Function Variant in MINPP1 Causes Pontocerebellar Hypoplasia with Characteristic Severe Neurodevelopmental Disorder" International Journal of Molecular Sciences 26, no. 11: 5213. https://doi.org/10.3390/ijms26115213
APA StyleAl-Maraghi, A., Shaath, R., Ford, K., Aamer, W., AlRayahi, J., Hussein, S., Aliyev, E., Agrebi, N., Kohailan, M., Hubrack, S. Z., Palaniswamy, S., Kennedy, A. D., DeBalsi, K. L., Elsea, S. H., Benini, R., Ben-Omran, T., Lo, B., Akil, A. S. A., & Fakhro, K. A. (2025). Biallelic Loss-of-Function Variant in MINPP1 Causes Pontocerebellar Hypoplasia with Characteristic Severe Neurodevelopmental Disorder. International Journal of Molecular Sciences, 26(11), 5213. https://doi.org/10.3390/ijms26115213