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NM_000291.4(PGK1):c.1132A>C (p.Thr378Pro) AND Glycogen storage disease due to phosphoglycerate kinase 1 deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 1, 2009
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000010634.6

Allele description [Variation Report for NM_000291.4(PGK1):c.1132A>C (p.Thr378Pro)]

NM_000291.4(PGK1):c.1132A>C (p.Thr378Pro)

Gene:
PGK1:phosphoglycerate kinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq21.1
Genomic location:
Preferred name:
NM_000291.4(PGK1):c.1132A>C (p.Thr378Pro)
Other names:
PGK Afula
HGVS:
  • NC_000023.11:g.78125344A>C
  • NG_008862.1:g.26176A>C
  • NM_000291.4:c.1132A>CMANE SELECT
  • NP_000282.1:p.Thr378Pro
  • NC_000023.10:g.77380841A>C
Protein change:
T378P; THR378PRO
Links:
OMIM: 311800.0015; dbSNP: rs137852539
NCBI 1000 Genomes Browser:
rs137852539
Molecular consequence:
  • NM_000291.4:c.1132A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Glycogen storage disease due to phosphoglycerate kinase 1 deficiency
Synonyms:
PGK1 DEFICIENCY; PHOSPHOGLYCERATE KINASE 1 DEFICIENCY WITH LEVO-DOPA-RESPONSIVE PARKINSONISM
Identifiers:
MONDO: MONDO:0010392; MedGen: C1970848; Orphanet: 713; OMIM: 300653

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000030860OMIM
no assertion criteria provided
Pathogenic
(Mar 1, 2009)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Levodopa Responsive Parkinsonism in Two Patients With Phosphoglycerate Kinase Deficiency.

Virmani T, Rotstein M, Spiegel R, Akman HO, DiMauro S, Greene PE.

Mov Disord Clin Pract. 2014 Sep;1(3):240-242. doi: 10.1002/mdc3.12055. No abstract available.

PubMed [citation]
PMID:
30713856
PMCID:
PMC6353531

Myopathic form of phosphoglycerate kinase (PGK) deficiency: a new case and pathogenic considerations.

Spiegel R, Gomez EA, Akman HO, Krishna S, Horovitz Y, DiMauro S.

Neuromuscul Disord. 2009 Mar;19(3):207-11. doi: 10.1016/j.nmd.2008.12.004. Epub 2009 Jan 20.

PubMed [citation]
PMID:
19157875

Details of each submission

From OMIM, SCV000030860.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In an 18-year-old man of Arab Bedouin descent with phosphoglycerate kinase-1 deficiency (300653), Spiegel et al. (2009) identified a c.1132A-C transversion in exon 10 of the PGK1 gene, resulting in a thr378-to-pro (T378P) substitution at a highly conserved residue. The patient had a myopathic phenotype, with onset of muscle cramps and exercise-induced pigmenturia at age 7 years. He had no evidence of hemolytic anemia or neurologic involvement; serum creatine kinase was increased. Protein structural analysis predicted that the mutation would destabilize an alpha-helix and interfere with the contact of domains responsible for proper catalytic interactions with nucleotide phosphates. Biochemical studies showed decreased PGK1 activity in muscle (0.9% of control values) and erythrocytes (1.6%). The patient's unaffected mother and 2 sisters were heterozygous for the mutation.

Virmani et al. (2014) published a clinical follow-up of the patient reported by Spiegel et al. (2009). Reported as patient 2 in the follow-up publication, the patient developed a unilateral hand tremor at 19 years of age, and over the next 2 years developed rigidity, bradykinesia, hypophonia, a slowed gait, and dysphagia. He was treated with L-dopa, which improved his symptoms, but increasing doses led to dyskinesia and rhabdomyolysis. At 21 years of age, he had unilateral hand resting and action tremor and asymmetric parkinsonism.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025