NM_018129.4(PNPO):c.69dup (p.His24fs) AND Pyridoxal phosphate-responsive seizures

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003617100.1

Allele description

NM_018129.4(PNPO):c.69dup (p.His24fs)

Gene:

PNPO:pyridoxamine 5'-phosphate oxidase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17q21.32

Genomic location:

Preferred name:

NM_018129.4(PNPO):c.69dup (p.His24fs)

HGVS:

NC_000017.11:g.47941744dup
NG_008744.1:g.5222dup
NM_018129.4:c.69dupMANE SELECT
NP_060599.1:p.His24fs
NC_000017.10:g.46019109_46019110insT
NC_000017.10:g.46019110dup

Protein change:

H24fs

Molecular consequence:

NM_018129.4:c.69dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Pyridoxal phosphate-responsive seizures (PNPOD)
Synonyms:: EPILEPTIC ENCEPHALOPATHY, NEONATAL, PNPO-RELATED; SEIZURES, PYRIDOXINE-RESISTANT, PLP-SENSITIVE; Pyridoxal 5'-phosphate-dependent epilepsy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012407; MedGen: C1864723; Orphanet: 79096; OMIM: 610090

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004506979	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15772097, 24645144, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004506979

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 27, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase.

Mills PB, Surtees RA, Champion MP, Beesley CE, Dalton N, Scambler PJ, Heales SJ, Briddon A, Scheimberg I, Hoffmann GF, Zschocke J, Clayton PT.

Hum Mol Genet. 2005 Apr 15;14(8):1077-86. Epub 2005 Mar 16.

PubMed [citation]

PMID:: 15772097

Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome.

Mills PB, Camuzeaux SS, Footitt EJ, Mills KA, Gissen P, Fisher L, Das KB, Varadkar SM, Zuberi S, McWilliam R, Stödberg T, Plecko B, Baumgartner MR, Maier O, Calvert S, Riney K, Wolf NI, Livingston JH, Bala P, Morel CF, Feillet F, Raimondi F, et al.

Brain. 2014 May;137(Pt 5):1350-60. doi: 10.1093/brain/awu051. Epub 2014 Mar 18.

PubMed [citation]

PMID:: 24645144
PMCID:: PMC3999720

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004506979.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.His24Serfs*26) in the PNPO gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PNPO are known to be pathogenic (PMID: 15772097, 24645144). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PNPO-related conditions. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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