Abstract
Background
The inositol polyphosphate 4-phosphatase intracellular signaling pathway is susceptible
to genetic or epigenetic alterations that may result in major neurological illnesses
with clinically significant pons and cerebellum involvement.
Case reports
A seven-year-old girl with pontocerebellar hypoplasia, resistant myoclonic epilepsy
with axial hypotonia, microcephaly, atypical facial appearance, nystagmus, ophthalmoplegia,
hyperactive tendon reflexes, spasticity, clonus, extensor plantar response, contractures
in wrists and ankles and growth retardation, whole-exome sequencing was performed
and a homozygous “NM_001134225.2:c.646C > T, p.(Arg216Ter)” variant was found in the
INPP4A gene.
Conclusion
INPP4A mutations should be kept in mind in cases with severely delayed psychomotor development,
progressive microcephaly, resistant myoclonic epilepsy, isolated cerebellum, and pons
involvement.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Brain and DevelopmentAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Phosphoinositides in cell regulation and membrane dynamics.Nature. 2006; 443: 651-657
- Inositol phosphatase INPP4A inhibits the apoptosis of in vitro neurons with characteristic of intractable epilepsy by reducing intracellular Ca(2+) concentration.Int J Clin Exp Pathol. 2018; 11: 1999-2007
- Inositol polyphosphate phosphatases in human disease.Curr Top Microbiol Immunol. 2012; 362: 247-314
- Assignment of the inositol polyphosphate 4-phosphatase type I gene (INPP4A) to human chromosome band 2q11.2 by in situ hybridization.Cytogenet Cell Genet. 1999; 87: 276-277
- Identification of a novel spliceoform of inositol polyphosphate 4-phosphatase type Ialpha expressed in human platelets: structure of human inositol polyphosphate 4-phosphatase type I gene.Biochem Biophys Res Commun. 2001; 286: 119-125
- The isolation and characterization of cDNA encoding human and rat brain inositol polyphosphate 4-phosphatase.J Biol Chem. 1995; 270: 16128-16133
- A null mutation in inositol polyphosphate 4-phosphatase type I causes selective neuronal loss in weeble mutant mice.Neuron. 2001; 32: 203-212
- A genetic variation in inositol polyphosphate 4 phosphatase a enhances susceptibility to asthma.Am J Respir Crit Care Med. 2008; 177: 712-719
- The PtdIns(3,4)P(2) phosphatase INPP4A is a suppressor of excitotoxic neuronal death.Nature. 2010; 465: 497-501
- Pontocerebellar hypoplasia.Am J Med Genet C Semin Med Genet. 2014; 166C: 173-183
- Hindbrain malformation and myoclonic seizures associated with a deleterious mutation in the INPP4A gene.Neurogenetics. 2015; 16: 23-26
- Whole exome sequencing identified a novel nonsense INPP4A mutation in a family with intellectual disability.Eur J Med Genet. 2020; 63103846
Article info
Publication history
Published online: February 07, 2023
Accepted:
January 26,
2023
Received in revised form:
January 24,
2023
Received:
July 22,
2022
Identification
Copyright
© 2023 Published by Elsevier B.V. on behalf of The Japanese Society of Child Neurology. All rights reserved.
