NM_000277.3(PAH):c.1A>G (p.Met1Val) AND Hyperphenylalaninemia, non-pku

Clinical significance:Pathogenic (Last evaluated: Jul 1, 1992)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000000617.5

Allele description [Variation Report for NM_000277.3(PAH):c.1A>G (p.Met1Val)]

NM_000277.3(PAH):c.1A>G (p.Met1Val)

Gene:
PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_000277.3(PAH):c.1A>G (p.Met1Val)
Other names:
NM_000277.2(PAH):c.1A>G
HGVS:
  • NC_000012.12:g.102917130T>C
  • NG_008690.2:g.46281A>G
  • NM_000277.3:c.1A>GMANE SELECT
  • NM_001354304.2:c.1A>G
  • NP_000268.1:p.Met1Val
  • NP_001341233.1:p.Met1Val
  • NC_000012.11:g.103310908T>C
  • NM_000277.1:c.1A>G
Protein change:
M1V; MET1VAL
Links:
OMIM: 612349.0009; dbSNP: rs62514891
NCBI 1000 Genomes Browser:
rs62514891
Molecular consequence:
  • NM_000277.3:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_001354304.2:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_000277.3:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hyperphenylalaninemia, non-pku
Synonyms:
Hyperphenylalaninemia
Identifiers:
MedGen: C0751435; Human Phenotype Ontology: HP:0004923

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000020767OMIMno assertion criteria providedPathogenic
(Jul 1, 1992)
germlineliterature only

PubMed (3)
[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

Novel PKU mutation on haplotype 2 in French-Canadians.

John SW, Rozen R, Laframboise R, Laberge C, Scriver CR.

Am J Hum Genet. 1989 Dec;45(6):905-9.

PubMed [citation]
PMID:
2574002
PMCID:
PMC1683463

Time and space clusters of the French-Canadian M1V phenylketonuria mutation in France.

Lyonnet S, Melle D, de Braekeleer M, Laframboise R, Rey F, John SW, Berthelon M, Berthelot J, Journel H, Le Marec B, et al.

Am J Hum Genet. 1992 Jul;51(1):191-6.

PubMed [citation]
PMID:
1609797
PMCID:
PMC1682893
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000020767.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In 9 French Canadian patients with hyperphenylalaninemia (see PKU, 261600), John et al. (1989) demonstrated a novel mutation on 5 of the 18 mutant chromosomes: an A-to-G transition (met to val) in codon 1 (M1V), the translation-initiation codon. In all cases the mutation was associated with haplotype 2. A homozygote for this mutation had the PKU phenotype. In 1 proband it was inherited with the splice junction mutation in exon 12 (612349.0001) (on haplotype 3), conferring PKU. In 2 probands it was inherited with a mutation on haplotype 1, conferring PKU in 1 and non-PKU hyperphenylalaninemia in the other.

In contemporary families in France with classic PKU, Lyonnet et al. (1992) found the M1V mutation on 4 of 152 independent chromosomes. All of the French and Quebec M1V mutations occurred on RFLP haplotype 2. The contemporary mutant French chromosomes clustered in southern Brittany (Finistere Sud). Genealogic reconstruction of the Quebec families identified 53 shared ancestors and a center of diffusion in the Perche region in 17th century France. The 2 clusters in France, one historical and the other contemporary, are not incompatible if one assumes the possibility that settlers returned from Nouvelle France or moved from Perche to southern Brittany.

By expression analysis of the M1V mutation, John et al. (1992) demonstrated nondetectable levels of PAH protein and activity.

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

Last Updated: Sep 6, 2021

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