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FBP1 Gene Curation

FBP1 Gene Curation

Owned by Katherine Lafferty
Last updated: yesterday at 12:11 pm
3 min read

Gene-disease assertions not curated here (add link or write note):

Disease

Fructose-1,6-bisphosphatase deficiency

Disease

Fructose-1,6-bisphosphatase deficiency

Inheritance

Autosomal recessive

Prevalence

Orphanet

Medline Plus Genetics

 

Source:

GeneReviews- “Fructose-1,6-bisphosphatase deficiency is rare. Approximately 150 affected individuals have been reported to date.

An estimated prevalence of fructose-1,6-bisphosphatase deficiency is 1:350,000 in the Dutch population [Visser et al 2004] and <1:900,000 in the French population [Lebigot et al 2015]. The disorder may be more frequent in populations with higher rates of consanguinity [Santer et al 2016].”

Rapid or full curation?

Rapid
Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

ClinGen- Only dosage sensitivity curated: Gene Associated with Autosomal Recessive Phenotype (30)

GeneCC- AR fructose-1,6-bisphosphatase deficiency (Strong by Invitae, Genomics England PanelApp, and PanelApp Australia)

OMIM- AR Fructose-1,6-bisphosphatase deficiency

GeneReviews- Fructose-1,6-bisphosphatase deficiency NCBI - WWW Error Blocked Diagnostic

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

PMID 9382095 (Japanese cohort):

c.960_961insG variant reported in 7 individuals with FBPase deficiency defined by <10% of FBPase activity levels. 3 of these individuals were homozygous (1 consanguineous family) and the remained 4 were compound het. Frameshift variant in last exon, possible escaped NMD. Two segregations in two unrelated families (1 segregation each) for this variant. (score= 9.5 points)

c.530C>A (p.Ala177Asp)- Variant seen in trans with c.960_961insG in one proband. Only one allele in gnomAD v4. (0.5 point)

c.490G>A (p.Gly164Ser)- Variant seen in 3 probands in trans with with c.960_961insG. Segregated in 1 individual in two unrelated families (1.5 pts)

c.88G>T (p.Glu30Ter)- Homozygous in one consanguineous family(2 pts)

Additional papers with case reports and FBP1 variants identified:

  • PMID: 34687058 (French cohort)

  • PMID: 30927757 (Single case report- Korean)

  • PMID: 28776561 (Single case report- Chinese)

  • PMID: 10234608 (4 case reports, mixed ancestry but non-Japanese)

  • PMID: 25601412 (French cohort- Caucasian and N. African pts)

Segregation Evidence:

Case/Control Evidence:

Experimental Evidence:

Source:

Clinical Validity Points Total

 

Source:

Clinical Validity Classification

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Strong (12 pts)

Source:

Molecular Mechanism

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function / Gain of function / Dominant Negative

 

Penetrance

Complete (100%)

High (≥80%)

Moderate  (<80% and >20%)

Low (≤20%)

(list source/PMID)

 

Source:

Age of Onset

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

 

Severity

Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers.

 

Clinical Features

 

Sources:

HPO Terms

https://hpo.jax.org/app/

 

Gene SOPs & Notes

 LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant

Curation Summary

- The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited

 

Case ID, Curator name, Date, Jira ticket link

 

 

 

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