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NM_000161.3(GCH1):c.671A>G (p.Lys224Arg) AND Dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 22, 2002
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:
RCV002508114.8

Allele description [Variation Report for NM_000161.3(GCH1):c.671A>G (p.Lys224Arg)]

NM_000161.3(GCH1):c.671A>G (p.Lys224Arg)

Gene:
GCH1:GTP cyclohydrolase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q22.2
Genomic location:
Preferred name:
NM_000161.3(GCH1):c.671A>G (p.Lys224Arg)
HGVS:
  • NC_000014.9:g.54844099T>C
  • NG_008647.1:g.63726A>G
  • NM_000161.3:c.671A>GMANE SELECT
  • NM_001024024.2:c.671A>G
  • NM_001024070.2:c.627-230A>G
  • NM_001024071.2:c.627-1045A>G
  • NP_000152.1:p.Lys224Arg
  • NP_001019195.1:p.Lys224Arg
  • NC_000014.8:g.55310817T>C
  • NM_000161.2:c.671A>G
  • P30793:p.Lys224Arg
  • p.LYS224ARG
Protein change:
K224R; LYS224ARG
Links:
UniProtKB: P30793#VAR_002648; OMIM: 600225.0013; dbSNP: rs41298442
NCBI 1000 Genomes Browser:
rs41298442
Molecular consequence:
  • NM_001024070.2:c.627-230A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001024071.2:c.627-1045A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000161.3:c.671A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001024024.2:c.671A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive
Identifiers:
MONDO: MONDO:0100098; MedGen: CN322657

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000030087OMIM
no assertion criteria provided
Pathogenic
(Oct 22, 2002) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations.

Furukawa Y, Kish SJ, Bebin EM, Jacobson RD, Fryburg JS, Wilson WG, Shimadzu M, Hyland K, Trugman JM.

Ann Neurol. 1998 Jul;44(1):10-6.

PubMed [citation]
PMID:
9667588

Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome.

Leuzzi V, Carducci C, Carducci C, Cardona F, Artiola C, Antonozzi I.

Neurology. 2002 Oct 22;59(8):1241-3.

PubMed [citation]
PMID:
12391354

Details of each submission

From OMIM, SCV000030087.2

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

Description

See 600225.0012 and Furukawa et al. (1998).

Leuzzi et al. (2002) reported a consanguineous Italian family in which 5 members over 3 generations were affected with variable severity of dopa-responsive dystonia (128230) with features of a myoclonus-dystonia syndrome (see, e.g., 159900). The most severely affected individual was the proband, the son of first cousins, who developed progressive myoclonic jerky movements of his upper limbs, lower limbs, trunk, and face beginning at the age of 3 years. He also exhibited mild dystonic postures of the upper limbs and neck, mild bradykinesia, and lack of facial expression. Blood prolactin was elevated and CSF homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), and biopterin were reduced. Treatment with L-DOPA resulted in marked improvement. In 4 affected members who were tested, including the proband, Leuzzi et al. (2002) identified a heterozygous 671A-G missense mutation in the GCH1 gene, resulting in a lys224-to-arg (L224R) substitution.

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

Last Updated: Jun 23, 2024