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Fanconi anemia complementation group G(FANCG)

MedGen UID:
854017
Concept ID:
C3469527
Disease or Syndrome
Synonym: Fanconi anemia group G
 
Gene (location): FANCG (9p13.3)
 
Monarch Initiative: MONDO:0013565
OMIM®: 614082

Disease characteristics

Excerpted from the GeneReview: Fanconi Anemia
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA. [from GeneReviews]
Authors:
Parinda A Mehta  |  Christen Ebens   view full author information

Additional descriptions

From OMIM
Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650.  http://www.omim.org/entry/614082
From MedlinePlus Genetics
Fanconi anemia is a condition that affects many parts of the body. People with this condition may have bone marrow failure, physical abnormalities, organ defects, and an increased risk of certain cancers.

The major function of bone marrow is to produce new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infections; and platelets, which are necessary for normal blood clotting. Approximately 90 percent of people with Fanconi anemia have impaired bone marrow function that leads to a decrease in the production of all blood cells (aplastic anemia). 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 (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia). People with Fanconi anemia may also develop myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally.

More than half of people with Fanconi anemia have physical abnormalities. These abnormalities can involve irregular skin coloring such as unusually light-colored skin (hypopigmentation) or café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Other possible symptoms of Fanconi anemia include malformed thumbs or forearms and other skeletal problems including short stature; malformed or absent kidneys and other defects of the urinary tract; gastrointestinal abnormalities; heart defects; eye abnormalities such as small or abnormally shaped eyes; and malformed ears and hearing loss. People with this condition may have abnormal genitalia or malformations of the reproductive system. As a result, most affected males and about half of affected females cannot have biological children (are infertile). Additional signs and symptoms can include abnormalities of the brain and spinal cord (central nervous system), including increased fluid in the center of the brain (hydrocephalus) or an unusually small head size (microcephaly).

Individuals with Fanconi anemia have an increased risk of developing a cancer of blood-forming cells in the bone marrow called acute myeloid leukemia (AML) or tumors of the head, neck, skin, gastrointestinal system, or genital tract. The likelihood of developing one of these cancers in people with Fanconi anemia is between 10 and 30 percent.  https://medlineplus.gov/genetics/condition/fanconi-anemia

Clinical features

From HPO
Leukemia
MedGen UID:
9725
Concept ID:
C0023418
Neoplastic Process
A cancer of the blood and bone marrow characterized by an abnormal proliferation of leukocytes.
Myelodysplasia
MedGen UID:
10231
Concept ID:
C0026985
Congenital Abnormality
Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.
Thumb deformity
MedGen UID:
107901
Concept ID:
C0575897
Finding
An abnormal structure of the first digit of the hand.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Cafe au lait spots, multiple
MedGen UID:
396266
Concept ID:
C1861975
Disease or Syndrome
The presence of six or more cafe-au-lait spots.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Abnormality of chromosome stability
MedGen UID:
1631925
Concept ID:
C4551705
Cell or Molecular Dysfunction
A type of chromosomal aberration characterized by reduced resistance of chromosomes to change or deterioration.

Professional guidelines

PubMed

Rechitsky S, Kuliev A, San Ramon G, Tur-Kaspa I, Wang Y, Wang W, Wu X, Wang L, Leigh D, Cram DS
J Mol Diagn 2020 Feb;22(2):220-227. Epub 2019 Nov 18 doi: 10.1016/j.jmoldx.2019.10.001. PMID: 31751677

Curated

Fanconi Anemia Clinical Care Guidelines, Fifth Edition.

Recent clinical studies

Etiology

Shah A, George M, Dhangar S, Rajendran A, Mohan S, Vundinti BR
Mol Biol Rep 2021 Jan;48(1):585-593. Epub 2021 Jan 4 doi: 10.1007/s11033-020-06101-2. PMID: 33394227
Jeong E, Lee SG, Kim HS, Yang J, Shin J, Kim Y, Kim J, Schärer OD, Kim Y, Yeo JE, Kim HM, Cho Y
Nucleic Acids Res 2020 Apr 6;48(6):3328-3342. doi: 10.1093/nar/gkaa062. PMID: 32002546Free PMC Article
van Twest S, Murphy VJ, Hodson C, Tan W, Swuec P, O'Rourke JJ, Heierhorst J, Crismani W, Deans AJ
Mol Cell 2017 Jan 19;65(2):247-259. Epub 2016 Dec 13 doi: 10.1016/j.molcel.2016.11.005. PMID: 27986371
Mantere T, Haanpää M, Hanenberg H, Schleutker J, Kallioniemi A, Kähkönen M, Parto K, Avela K, Aittomäki K, von Koskull H, Hartikainen JM, Kosma VM, Laasanen SL, Mannermaa A, Pylkäs K, Winqvist R
Clin Genet 2015 Jul;88(1):68-73. Epub 2014 Jul 30 doi: 10.1111/cge.12447. PMID: 24989076
Yamashita T, Nakahata T
Int J Hematol 2001 Jul;74(1):33-41. doi: 10.1007/BF02982547. PMID: 11530803

Diagnosis

Shah A, George M, Dhangar S, Rajendran A, Mohan S, Vundinti BR
Mol Biol Rep 2021 Jan;48(1):585-593. Epub 2021 Jan 4 doi: 10.1007/s11033-020-06101-2. PMID: 33394227
Li N, Ding L, Li B, Wang J, D'Andrea AD, Chen J
Exp Hematol 2018 Oct;66:32-41.e8. Epub 2018 Jul 19 doi: 10.1016/j.exphem.2018.07.003. PMID: 30031030
Park J, Chung NG, Chae H, Kim M, Lee S, Kim Y, Lee JW, Cho B, Jeong DC, Park IY
Clin Genet 2013 Sep;84(3):271-5. doi: 10.1111/cge.12042. PMID: 23067021
Couch FJ, Johnson MR, Rabe K, Boardman L, McWilliams R, de Andrade M, Petersen G
Cancer Res 2005 Jan 15;65(2):383-6. PMID: 15695377
de Winter JP, Waisfisz Q, Rooimans MA, van Berkel CG, Bosnoyan-Collins L, Alon N, Carreau M, Bender O, Demuth I, Schindler D, Pronk JC, Arwert F, Hoehn H, Digweed M, Buchwald M, Joenje H
Nat Genet 1998 Nov;20(3):281-3. doi: 10.1038/3093. PMID: 9806548

Therapy

Xing L, Mi W, Zhang Y, Tian S, Zhang Y, Qi R, Lou G, Zhang C
J Cell Mol Med 2020 Sep;24(17):9839-9852. Epub 2020 Aug 6 doi: 10.1111/jcmm.15567. PMID: 32762026Free PMC Article
Yabar CS, Winter JM
Gastroenterol Clin North Am 2016 Sep;45(3):429-45. doi: 10.1016/j.gtc.2016.04.003. PMID: 27546841
Young A, Berry R, Holloway AF, Blackburn NB, Dickinson JL, Skala M, Phillips JL, Brettingham-Moore KH
BMC Cancer 2014 Nov 4;14:808. doi: 10.1186/1471-2407-14-808. PMID: 25369795Free PMC Article
van der Heijden MS, Brody JR, Dezentje DA, Gallmeier E, Cunningham SC, Swartz MJ, DeMarzo AM, Offerhaus GJ, Isacoff WH, Hruban RH, Kern SE
Clin Cancer Res 2005 Oct 15;11(20):7508-15. doi: 10.1158/1078-0432.CCR-05-1048. PMID: 16243825
Ferrer M, de Winter JP, Mastenbroek DC, Curiel DT, Gerritsen WR, Giaccone G, Kruyt FA
Cancer Gene Ther 2004 Aug;11(8):539-46. doi: 10.1038/sj.cgt.7700734. PMID: 15192709

Prognosis

Reyes P, García-de Teresa B, Juárez U, Pérez-Villatoro F, Fiesco-Roa MO, Rodríguez A, Molina B, Villarreal-Molina MT, Meléndez-Zajgla J, Carnevale A, Torres L, Frias S
Int J Mol Sci 2022 Feb 20;23(4) doi: 10.3390/ijms23042334. PMID: 35216452Free PMC Article
Shah A, George M, Dhangar S, Rajendran A, Mohan S, Vundinti BR
Mol Biol Rep 2021 Jan;48(1):585-593. Epub 2021 Jan 4 doi: 10.1007/s11033-020-06101-2. PMID: 33394227
Farah RA, Nair P, Koueik J, Yammine T, Khalifeh H, Korban R, Collet A, Khayat C, Dubois-Denghien C, Chouery E, Blanluet M, El-Hayek S, Stoppa-Lyonnet D, Megarbane A
J Pediatr Hematol Oncol 2021 Jul 1;43(5):e727-e735. doi: 10.1097/MPH.0000000000001909. PMID: 32947577
Yabe M, Koike T, Ohtsubo K, Imai E, Morimoto T, Takakura H, Koh K, Yoshida K, Ogawa S, Ito E, Okuno Y, Muramatsu H, Kojima S, Matsuo K, Mori M, Hira A, Takata M, Yabe H
Ann Hematol 2019 Feb;98(2):271-280. Epub 2018 Oct 27 doi: 10.1007/s00277-018-3517-0. PMID: 30368588
Mahato D, Samanta D, Mukhopadhyay SS, Krishnaraj RN
J Recept Signal Transduct Res 2017 Jun;37(3):276-282. Epub 2016 Sep 8 doi: 10.1080/10799893.2016.1225309. PMID: 27608133

Clinical prediction guides

Shah A, George M, Dhangar S, Rajendran A, Mohan S, Vundinti BR
Mol Biol Rep 2021 Jan;48(1):585-593. Epub 2021 Jan 4 doi: 10.1007/s11033-020-06101-2. PMID: 33394227
Jeong E, Lee SG, Kim HS, Yang J, Shin J, Kim Y, Kim J, Schärer OD, Kim Y, Yeo JE, Kim HM, Cho Y
Nucleic Acids Res 2020 Apr 6;48(6):3328-3342. doi: 10.1093/nar/gkaa062. PMID: 32002546Free PMC Article
Mantere T, Haanpää M, Hanenberg H, Schleutker J, Kallioniemi A, Kähkönen M, Parto K, Avela K, Aittomäki K, von Koskull H, Hartikainen JM, Kosma VM, Laasanen SL, Mannermaa A, Pylkäs K, Winqvist R
Clin Genet 2015 Jul;88(1):68-73. Epub 2014 Jul 30 doi: 10.1111/cge.12447. PMID: 24989076
Park J, Chung NG, Chae H, Kim M, Lee S, Kim Y, Lee JW, Cho B, Jeong DC, Park IY
Clin Genet 2013 Sep;84(3):271-5. doi: 10.1111/cge.12042. PMID: 23067021
Chu PC, Wang TY, Lu YT, Chou CK, Yang YC, Chang MS
Carcinogenesis 2009 Oct;30(10):1710-6. Epub 2009 Sep 11 doi: 10.1093/carcin/bgp204. PMID: 19748926

Supplemental Content

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    • PubMed
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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • FARF, 2020
      Fanconi Anemia Clinical Care Guidelines, Fifth Edition.

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