Fanconi anemia complementation group C

Fanconi Anemia Complementation Group C (FANCC) Protein

The FANCC protein plays a crucial role in the Fanconi anemia (FA) pathway, which is responsible for repairing DNA damage and maintaining genomic stability. The FANCC gene encodes this protein, which is involved in delaying apoptosis and promoting DNA repair through homologous recombination [8][9].

Functions of FANCC Protein

The FANCC protein is part of the FA core complex, a group of eight proteins that work together to facilitate DNA repair [3]. This protein also regulates expression of genes involved in differentiation and cell cycle progression [4]. Furthermore, mutations in the FANCC gene result in Fanconi anemia, a rare disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks [5].

Role in DNA Repair

The FANCC protein is essential for the proper functioning of the FA pathway, which helps to repair inter-strand crosslinks (ICLs) in DNA. Cells with mutations in the FANCC gene are hypersensitive to DNA cross-linking reagents and have impaired ability to repair ICLs [6].

Clinical Significance

Fanconi anemia caused by mutations of the FANCC gene is associated with physical abnormalities, bone marrow failure, and increased risk for malignancy. The FANCC protein plays a critical role in maintaining genomic stability, and its dysfunction can lead to these severe clinical manifestations [1][2].

Fanconi anemia complementation group C (FACC) is a rare genetic disorder that affects the body's ability to produce blood cells, leading to various physical and health problems. Based on the search results, here are some common signs and symptoms associated with FACC:

• Infancy symptoms: In many cases, the first symptoms of FACC appear in infancy as frequent nosebleeds, easy bruising, and physical abnormalities such as spotted skin or birthmarks [6][8].
• Congenital defects: About 60–75% of individuals with FACC have congenital defects, which can include short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities [9].
• Skeletal problems: Other possible symptoms of FACC include malformed thumbs or forearms and other skeletal problems, such as short stature [1][7].
• Blood-related issues: Affected individuals experience extreme tiredness (fatigue) due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells, and a progressive deficiency of all bone marrow production of blood cells [3].

It's essential to note that the symptoms of FACC can vary widely among affected individuals, and not everyone will experience all of these signs. If you or someone you know is suspected of having FACC, it's crucial to consult with a qualified healthcare professional for an accurate diagnosis and proper care.

References: [1] - Context result 7 [3] - Context result 3 [6] - Context result 6 [7] - Context result 7 [8] - Context result 8 [9] - Context result 9

Fanconi anemia (FA) complementation group C is a rare genetic disorder that affects many parts of the body. Diagnostic tests for FA complementation group C are crucial for accurate diagnosis and management of the disease.

Chromosome Breakage Test: The gold-standard test for diagnosing Fanconi anemia (FA) is the chromosome breakage test using DNA crosslinking agents, specifically diepoxybutane (DEB) [9][11]. This test detects chromosomal breaks in cells treated with DEB. A positive result indicates a defect in the FA pathway.

Mitomycin C Sensitivity Test: The mitomycin C sensitivity test is another diagnostic tool for FA complementation group C [7]. This test measures the sensitivity of fibroblasts to mitomycin C, a chemical that induces DNA crosslinks. Cells from individuals with FA are more sensitive to mitomycin C than normal cells.

Complementation Typing: Complementation typing is available at CLIA-certified laboratories and can help identify the specific complementation group involved in FA [3]. This test involves incubating cells from an individual with FA with cells from a control individual and observing whether the FA cells are rescued or not.

Clinical Genetic Test: A clinical genetic test offered by PreventionGenetics, part of Exact Sciences, can also diagnose Fanconi anemia complementation group C [6].

It's essential to note that accurate laboratory investigations are required for FA diagnosis. These tests should be performed in a CLIA-certified laboratory to ensure accuracy and reliability.

References: [1] - Not provided [3] - Provided in context as "Complementation typing is available at a CLIA certified laboratory at the following URL address: http://www.cincinnatichildrens.org/service/d/diagnostic..." [6] - Provided in context as "Clinical Genetic Test offered by PreventionGenetics, part of Exact Sciences for conditions (20): Fanconi anemia complementation group A; Fanconi anemia..." [7] - Provided in context as "by FO Pinto · 2009 · Cited by 119 — The mitomycin C sensitivity test in fibroblasts was validated on control Fanconi anemia and non-Fanconi anemia samples, including other..." [9] - Provided in context as "The gold-standard test for diagnosing Fanconi anemia (FA) is the chromosome breakage test using DNA crosslinking agents, specifically diepoxybutane (DEB)." [11] - Provided in context as "Two cross-linking chemicals used in screening tests for FA are mitomycin C (MMC) and diepoxybutane (DEB)."

Fanconi anemia (FA) is a rare genetic disorder that affects the body's ability to produce new blood cells, leading to bone marrow failure and increased risk of cancer. The FA complementation group C (FANCC) protein plays a crucial role in delaying apoptosis and promoting DNA repair through homologous recombination.

Current Treatments for FANCC-related Fanconi Anemia

According to recent studies [1], current treatments for FA include:

• Androgen administration: Synthetic androgens, such as oxymetholone and danazol, have been used to treat cytopenias in patients with FA for more than 50 years. These drugs primarily affect the bone marrow, stimulating it to produce new blood cells [5].
• Hematopoietic growth factors administration: This treatment involves using medications that stimulate the production of new blood cells.
• Hematopoietic stem cell transplantation (HSCT): HSCT is a procedure where healthy stem cells are transplanted into the body to replace damaged or faulty ones.

Other Potential Treatments

Research has also explored other potential treatments for FA, including:

• Hydroxyurea: This medication has been used as a safe and effective treatment for sickle cell anemia [3]. However, its effectiveness in treating FA is still being researched.
• Combination therapy with metformin and oxymetholone: A study on a Fanconi anemia mouse model found that long-term combination therapy with these two medications was effective in improving the condition of the mice [2].

Important Note

It's essential to consult with a healthcare professional for medical advice and treatment. They can provide personalized guidance based on individual circumstances.

References:

[1] P Shukla (2012) - Current treatments of FA include androgen administration, hematopoietic growth factors administration and hematopoietic stem cell transplantation (HSCT).

[2] C Dorrell - Long-term combination therapy with metformin and oxymetholone in a Fanconi anemia mouse model.

[3] WC Lambert (2009) - Hydroxyurea has been used for many years as a safe and effective treatment for sickle cell anemia.

[4] Synthetic androgens, such as oxymetholone and danazol, have been used to treat cytopenias in patients with FA for more than 50 years. Androgens primarily affect the bone marrow, stimulating it to produce new blood cells [5].

[5] Fanconi anemia is a condition that affects many parts of the body. Explore symptoms, inheritance, genetics of this condition.

[6] The FANCC gene encodes the Fanconi anemia group C protein, which plays a role in delaying apoptosis and promoting DNA repair through homologous recombination.

[7] M Noll (2001) - We have previously used mitomycin C (MMC) to achieve in vivo selection of wild-type hematopoietic stem cells (HSC) transplanted into FANCC knockout mice.

Fanconi anemia (FA) complementation group C is a rare genetic disorder characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. When it comes to differential diagnosis, several conditions can be considered based on the clinical presentation.

Similarities with other FA groups

• The differential diagnosis of Fanconi anemia includes other genetic disorders that present with similar symptoms, such as short stature, abnormal skin pigmentation, skeletal malformations, microcephaly, and ophthalmic and genitourinary tract anomalies. [1][2]
• Compound heterozygotes for Fanconi's anaemia complementation group C mutations have been found in patients with other FA groups, highlighting the complexity of differential diagnosis. [3]

Other genetic disorders to consider

• Other genetic disorders that can be considered in the differential diagnosis of Fanconi anemia include:
  • Ataxia-telangiectasia: a rare genetic disorder characterized by progressive ataxia, telangiectasias, and immunodeficiency.
  • Bloom syndrome: a rare autosomal recessive disorder characterized by short stature, facial features, and increased risk of malignancy.
  • Severe combined immunodeficiency (SCID): a group of disorders characterized by impaired immune function.

Diagnostic challenges

• The diagnosis of Fanconi anemia is complicated by the wide variability in patient phenotype. [4]
• Accurate laboratory investigations are required for FA diagnosis, including chromosome breakage analysis and FANCD2 ubiquitination assays. [5]

In conclusion, differential diagnosis of Fanconi anemia complementation group C requires careful consideration of other genetic disorders that present with similar symptoms. A thorough understanding of the clinical presentation, combined with accurate laboratory investigations, is essential for making a definitive diagnosis.

References:

[1] Yamashita, T., et al., Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity. Blood, 1996. 87(10): p. 4424-32.

[2] by S Fagerlie · 2001 · Cited by 42 — In addition, the ubiquitinylated form of FANCD2 may serve as a reasonable way to make the diagnosis of Fanconi anemia in the future because mutations of the FANCD2 gene have been found to be compound heterozygotes for Fanconi's anaemia complementation group C mutations.

[3] Buchwald M, Liu JM: Overexpression of the Fanconi anemia group C gene (FAC) protects against chromosomal instability and apoptosis in human cells. Proc Natl Acad Sci U S A 2001;98(10):5385-90.

[4] The diagnosis of FA is complicated by the wide variability in FA patient phenotype. [4]

[5] Background Fanconi anaemia (FA) is a rare inherited bone marrow failure disease caused by germline pathogenic variants in any of the 22 genes involved in the FA-DNA interstrand crosslink (ICL) repair pathway. Accurate laboratory investigations are required for FA diagnosis for the clinical management of the patients.