Hereditary Hypofibrinogenemia with Hepatic Storage

• Main Authors: Rosanna Asselta, Elvezia Maria Paraboschi, Stefano Duga
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: International Journal of Molecular Sciences
• Subjects: fibrinogen; <i>FGG</i> gene; hypofibrinogenemia; storage disease; hereditary hypofibrinogenemia with hepatic storage; mutation
• Online Access: https://www.mdpi.com/1422-0067/21/21/7830
• ISSN: 1661-6596; 1422-0067

Fibrinogen is a 340-kDa plasma glycoprotein constituted by two sets of symmetrical trimers, each formed by the Aα, Bβ, and γ chains (respectively coded by the <i>FGA</i>, <i>FGB</i>, and <i>FGG</i> genes). Quantitative fibrinogen deficiencies (hypofibrinogenemia, afibrinogenemia) are rare congenital disorders characterized by low or unmeasurable plasma fibrinogen antigen levels. Their genetic basis is represented by mutations within the fibrinogen genes. To date, only eight mutations, all affecting a small region of the fibrinogen γ chain, have been reported to cause hereditary hypofibrinogenemia with hepatic storage (HHHS), a disorder characterized by protein aggregation in the endoplasmic reticulum, hypofibrinogenemia, and liver disease of variable severity. Here, we will briefly review the clinic characteristics of HHHS patients and the histological feature of their hepatic inclusions, and we will focus on the molecular genetic basis of this peculiar type of coagulopathy.