Bleeding and Platelet Disorders

Gene: FGA

Green List (high evidence)

Bleeding due to afibrinogenaemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial haemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen.

Monoallelic variants in this gene are associated with amyloidosis.

- Premature termination variants (PTVs) located downstream of ~p.500 are associated with autosomal dominant familial visceral amyloidosis (MIM#105200). PTVs located upstream are associated with autosomal recessive congenital afibrinogenemia (MIM#202400). (PMIDs: 31064749, 17295221, 19073821)
- Biallelic loss of function result in congenital afibrinogenemia (MIM#202400) (PMID:17295221). The disease mechanism of autosomal dominant familial visceral amyloidosis (MIM#105200) is unclear.
- PMID:11739173 concluded that null mutants of congenital afibrinogenemia (AR) patients escaped NMD.

Created: 18 May 2021, 1:06 a.m. | Last Modified: 18 May 2021, 1:06 a.m.

Panel Version: 0.220

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Afibrinogenemia, congenital (MIM#202400)

Publications

• 31064749
• 17295221
• 19073821
• 11739173

Green List (high evidence)

- Premature termination variants (PTVs) located downstream of ~p.500 are associated with autosomal dominant familial visceral amyloidosis (MIM#105200). PTVs located upstream are associated with autosomal recessive congenital afibrinogenemia (MIM#202400). (PMIDs: 31064749, 17295221, 19073821)
- Biallelic loss of function result in congenital afibrinogenemia (MIM#202400) (PMID:17295221). The disease mechanism of autosomal dominant familial visceral amyloidosis (MIM#105200) is unclear.
- PMID:11739173 concluded that null mutants of congenital afibrinogenemia (AR) patients escaped NMD.

Created: 17 May 2021, 10:02 a.m. | Last Modified: 17 May 2021, 10:02 a.m.

Panel Version: 0.7637

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Afibrinogenemia, congenital (MIM#202400), AR; Amyloidosis, familial visceral (MIM#105200), AD

Publications

• 31064749
• 17295221
• 19073821
• 11739173

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