Primary Ovarian Insufficiency_Premature Ovarian Failure

STR: FXPOI

Green List (high evidence)

Chromosome: X
GRCh37 Position: 146993569-146993628
GRCh38 Position: 147912051-147912110
Repeated Sequence: CGG
Normal Number of Repeats: < or = 44
Pathogenic Number of Repeats: = or > 55

FMR1 (fragile X mental retardation 1)
EnsemblGeneIds (GRCh38): ENSG00000102081
EnsemblGeneIds (GRCh37): ENSG00000102081
OMIM: 309550, Gene2Phenotype
FMR1 is in 11 panels

1 review

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

HGVS nomenclature - NM_002024.5:c.-129_-127CGG[X]
RNA-mediated toxicity may result in the POI phenotype, whereas loss of function through methylation silencing of FMR1 is associated with the FXS phenotype.
Intermediate (gray zone, inconclusive, borderline): ~45 to ~54 repeats
Premutation - risk of FXPOI: ~55 to ~200 repeats
Full mutation - fragile X syndrome (FXS): >200 repeats
It is estimated that 21% of women who carry a premutation develop FXPOI. The association between repeat size of the premutation allele and FXPOI is nonlinear; women with 80-99 repeats are at greatest risk for FXPOI.
Sources: Expert list
Created: 11 Dec 2020, 5:49 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Premature ovarian failure 1 MIM#311360

Publications

Variants in this STR are reported as part of current diagnostic practice

Clinically Relevant

Interruptions in the repeated sequence are reported as part of standard diagnostic practise

Details

Name
FXPOI
Chromosome
X
GRCh37 Coordinates
146993569-146993628
GRCh38 Coordinates
147912051-147912110
Repeated Sequence
CGG
Normal Number of Repeats: < or =
44
Pathogenic Number of Repeats: = or >
55
Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Premature ovarian failure 1 MIM#311360
Tags
5'UTR
OMIM
309550
Clinvar variants
Variants in FMR1
Penetrance
None
Publications

History Filter Activity

11 Dec 2020, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Str: fxpoi has been classified as Green List (High Evidence).

11 Dec 2020, Gel status: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

STR: FXPOI was added STR: FXPOI was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Expert list 5'UTR tags were added to STR: FXPOI. Mode of inheritance for STR: FXPOI was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for STR: FXPOI were set to 20301558 Phenotypes for STR: FXPOI were set to Premature ovarian failure 1 MIM#311360 Review for STR: FXPOI was set to GREEN STR: FXPOI was marked as clinically relevant STR: FXPOI was marked as current diagnostic