Hereditary Hypofibrinogenemia with Hepatic Storage
Abstract
:1. Fibrinogen and Related Disorders
1.1. Brief Overview on Biosynthesis, Structure, and Function of Fibrinogen
1.2. Fibrinogen-Related Inherited Disorders
2. Hereditary Hypofibrinogenemia with Hepatic Storage (HHHS)
2.1. Brief Historical Notes on HHHS
2.2. Histologic Characteristics of HHHS Inclusions
2.3. Clinic Characteristics of HHHS Patients
2.4. Genetic Basis of HHHS
2.5. Prevalence of HHHS Mutations Worldwide
2.6. Molecular Mechanisms
3. Open Questions and Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
Aα | A alpha polypeptide chain |
ALT | Alanine Aminotransferase |
APOB | Apolipoprotein B |
APTT | Activated Partial Thromboplastin Time |
AST | Aspartate Aminotransferase |
Bβ | B beta polypeptide chain |
CBZ | Carbamazepine |
ChinaMAP | China Metabolic Analytics Project |
CNX | Calnexin |
COVID-19 | Coronavirus Disease 2019 |
CRT | Calreticulin |
ER | Endoplasmic Reticulum |
ERp57 | Endoplasmic Reticulum Resident Protein 57 (protein disulfide isomerase homologue) |
ERSD | Endoplasmic Reticulum Storage Diseases |
γ | Gamma polypeptide chain |
FGA | Fibrinogen Alpha Chain Gene |
FGB | Fibrinogen Beta Chain Gene |
FGG | Fibrinogen Gamma Chain Gene |
FSD | Fibrinogen Storage Disease |
GME | Greater Middle East |
GnomAD | Genome Aggregation Database |
GTex | Genotype-Tissue Expression |
HHHS | Hereditary Hypofibrinogenemia with Hepatic Storage |
HFSD | Hepatic Fibrinogen Storage Disease |
INR | International Normalized Ratio |
MTTP | Microsomal Triglyceride Transfer Protein |
PT | Prothrombin Time |
PTT | Partial Thromboplastin Time |
RCL | Reactive Centre Loop |
SARS-CoV-2 | Severe Acute Respiratory Syndrome Coronavirus-2 |
TCT | Thrombin Clotting Time |
UDCA | Ursodeoxycholic Acid |
∆∆G | Protein Folding Free Energy Change |
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Mutant Fibrinogen 1 | Country of Origin of the Index Case 1 | Sex | Age (Years) | ALT/AST 2 | Fibrinogen Levels (mg/dL) 3 | Other Coagulation Parameters | Liver Disease | Reference |
---|---|---|---|---|---|---|---|---|
Brescia | Italy * | M | 64 | Transaminase elevation | Clauss = 20 Immunoreactive = 100 | TCT = 47 sec | Cirrhosis | [26] |
Italy | F | 49 | n.r. | 20 | n.r. | Cirrhosis | [28] | |
Caucasian | M | 5 | Elevated ALT | n.r. | n.r. | Mild liver disease | [29] | |
AI DuPont | US * | M | 4 | 94/67 | Functional = 47 | PT = 15.3 sec INR = 1.5 | Mild focal portal inflammatory infiltrate | [30] |
Pisa | Italy * | F | 3 | 169/105 | Functional = 117 Antigenic = 136 | APTT = 33.7 sec TCT = 48 sec | No sign of liver disease | [31] |
Ankara | Turkey * | F | 5.5 | 46/55 | 55 | PT = 14 sec PTT = 24 sec INR = 1.2 TCT = 15 sec | No sign of liver disease | [32] |
Angers | France * | F | 35 | 73/51 | Functional = 96 Antigenic = 123 | PT = 18.4 sec | Severe chronic liver disease | [33] |
Beograd | Serbia * | M | 3 | 308/187 | Functional = 66 Antigenic = 95 | PT = 62.8 sec APTT = 38.2 sec TCT = 28.3 sec | No sign of liver disease | [31] |
Trabzon | Turkey * | M | 3.5 | 252/144 | Clauss = 36.8 | PT = 19.34 sec APTT = 35.7 sec INR = 1.69 | No sign of liver disease | [34] |
Aguadilla | Puerto Rico * | F | 3 | 104/- | Clauss = 60 | PT = 17.1 sec | No sign of liver disease | [35] |
Turkey | F | 2 | 151/77 | 74 | PT = 14.8 PTT = 26 sec INR = 1.27 | Portal and septal fibrosis | [28] | |
Turkey | F | 5 | 223/411 | 48 | PT = 13.4 sec PTT = 25 sec | Advanced liver fibrosis | [36] | |
Italy | M | 4 | n.r. | 43 | n.r. | Septal fibrosis | [28] | |
Japan | M | 2 | 200/190 | 37.6 | PT = 61.1% (n.v., 70–120%) APTT = 32 sec | Early cirrhosis | [37] | |
Switzerland | M | 61 | 131/109 | 70–80 | PT = 16.5 sec INR = 1.41 | No sign of chronic liver disease; portal hypertension | [38] | |
Italy | M | 6 | 280/110 | Clauss = 57 | PT = 49% (n.v., 70–120%) PTT = 42 sec | Chronic liver disease | [39] | |
Caucasian | F | 6 | Elevated ALT | n.r. | PT = prolonged | Mild liver disease | [29] | |
Siria | F | 3 | 250/185 | 89 | PTT = 40 sec INR = 1 | Hepatomegaly | [40] | |
Switzerland | F | 4.5 | 125/111 | Clauss = 70 Immunoreactive < 120 | n.r. | Mild liver disease | [41] | |
China | M | 2 | 529.6/298.2 | 29 | PT = 17.1 sec APTT = 42.8 sec | Portal fibrosis and mild hepatitis | [42] | |
China | M | 4 | 122/119 | Clauss = 64 | PT = 17.1 sec APTT = 43 sec INR = 1.38 | Hepatomegaly | [43] |
Mutant Fibrinogen | Country 1 | FGG Exon | Type of Mutation | Chr 4 Position 2 | Nt Variation | Native Protein | Mature Protein | Status | Reference |
---|---|---|---|---|---|---|---|---|---|
Brescia | Italy | 8 | Missense | 155,528,058 | G > C | p.Gly310Arg | p.Gly284Arg | Heterozygous | [26] |
AI DuPont | US | 8 | Missense | 155,527,968 | C > A | p.Thr340Pro | p.Thr314Pro | Heterozygous | [30] |
Pisa | Italy | 8 | Missense | 155,527,962 | G > A | p.Asp342Asn | p.Asp316Asn | Heterozygous | [31] |
Ankara | Turkey | 8 | Missense | 155,527,890 | C > G | p.His366Asp | p.His340Asp | Heterozygous | [32] |
Angers | France | 8 | Deletion + Splicing | 155,527,856–155,527,869 | GTTTATTACCAAGG deletion | p.delGVYYQ 372–376 | p.delGVYYQ 346–350 | Heterozygous | [33] |
Beograd | Serbia | 9 | Missense | 155,526,174 | G > A | p.Gly392Ser | p.Gly366Ser | Heterozygous | [31] |
Trabzon | Turkey | 9 | Missense | 155,526,159 | C > T | p.Thr397Ile | p.Thr371Ile | Heterozygous | [34] |
Aguadilla | Puerto Rico | 9 | Missense | 155,526,147 | C > T | p.Arg401Trp | p.Arg375Trp | Heterozygous | [35] |
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Asselta, R.; Paraboschi, E.M.; Duga, S. Hereditary Hypofibrinogenemia with Hepatic Storage. Int. J. Mol. Sci. 2020, 21, 7830. https://doi.org/10.3390/ijms21217830
Asselta R, Paraboschi EM, Duga S. Hereditary Hypofibrinogenemia with Hepatic Storage. International Journal of Molecular Sciences. 2020; 21(21):7830. https://doi.org/10.3390/ijms21217830
Chicago/Turabian StyleAsselta, Rosanna, Elvezia Maria Paraboschi, and Stefano Duga. 2020. "Hereditary Hypofibrinogenemia with Hepatic Storage" International Journal of Molecular Sciences 21, no. 21: 7830. https://doi.org/10.3390/ijms21217830