Fanconi Anemia, Complementation Group A

Alternative Names

  • FANCA
  • Fanconi Anemia
  • FA
  • Fancomi Anemia, Estren-Dameshek Variant
  • Estren-Dameshek Variant of Fancomi Anemia
  • Estren-Dameshek Variant of Fanconi Pancytopenia
  • Estren-Dameshek Variant of Fanconi Pancytopenia Type 1
  • FA1
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WHO-ICD-10 version:2010

Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism

Aplastic and other anaemias

OMIM Number

227650

Mode of Inheritance

Autosomal recessive with at least two loci and possibly multiple alleles

Gene Map Locus

16q24.3

Description

Fanconi anemia is the most common of the inherited anemias and is associated with chromosomal instability. It occurs at a rate of 1/350,000 births, with a carrier frequency estimated to approximately 1 per 300 population. Clinically, it is characterized by diverse congenital abnormalities, bone marrow failure, and increased predisposition to develop acute myeloid leukaemia. Affected individuals appear normal and may not be diagnosed until hematopoiesis is compromised, which is usually not apparent before the age of 5-10 years.

Fanconi anemia is genetically heterogeneous. It is caused by mutation in one of the nine complementation groups identified thus far, referred to as FA-A, -B, -C, -D1, -D2, -E, -F, -G and -L. Most of the Fanconi anemia patients belong to complementation group FA-A due to mutations in the Fanconi anemia complementation group A (FANCA) gene. Recent studies suggest that the Fanconi anemia pathway of genome stabilization may be controlled by at least 11 different genes, including FANCI and FANCJ.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
227650.1LebanonMale Chromosomal breakage induced by crosslin...NM_000135.4:c.3491C>THomozygousAutosomal, RecessiveFarah et al. 2020
227650.2LebanonMale Thrombocytopenia; Anemia; Multiple caf...NM_000135.4:c.4261-19_4261-12del, NM_000135.4:c.2852G>AHeterozygousAutosomal, RecessiveFarah et al. 2020
227650.3LebanonMaleYes Thrombocytopenia; Anemia; Preaxial pol...NM_000135.4:c.2602-2A>GHomozygousAutosomal, RecessiveFarah et al. 2020
227650.4LebanonMaleYes Thrombocytopenia; Splenomegaly; Chromo...NM_000135.4:c.2602-2A>GHomozygousAutosomal, RecessiveFarah et al. 2020
227650.5LebanonMaleYes Chromosomal breakage induced by crosslin...NM_000135.4:c.2107C>T, NM_000135.4:c.4249C>GHomozygousAutosomal, RecessiveFarah et al. 2020
227650.6LebanonMale Dilated cardiomyopathy; Hearing impairm...NM_000135.4:c.4261-2A>C, NM_000135.4:c.688G>AHomozygousAutosomal, RecessiveFarah et al. 2020
227650.7LebanonFemaleYesYes Chromosomal breakage induced by crosslin...NM_000135.4:c.190-1G>CHomozygousAutosomal, RecessiveFarah et al. 2020
227650.8LebanonMaleYes Thrombocytopenia; Anemia; Multiple caf...NM_000135.4:c.190-1G>CHomozygousAutosomal, RecessiveFarah et al. 2020
227650.9LebanonFemale Absent radius; Absent thumb; Microceph...NM_000135.4:c.3518G>AHomozygousFarah et al. 2020

Other Reports

Egypt

Tamary et al. (2000) studied an Ashkenazi/Egyptian Fanconi anemia patient. However, the mutation in one FANCA allele could not be identified.

Iraq

Tamary et al. (2000) studied an Iraqi-Jewish Fanconi anemia patient. They could not identify any mutations in the two FANCA alleles of this patient.

[See also: Morocco > Tamary et al., 2000].

Kuwait

Mohammed (1994) described a girl child with Fanconi Anemia born to consanguineous parents. The child had multiple congenital anomalies including microcephaly, short neck, high arched palate, VSD, polydactyly, and bilateral simian creases. Bone marrow biopsy suggested acute lymhoblastic leukemia. Karyotype analysis of peripheral blood revealed multiple chromosomal abnormalities, mostly in chromosomes 1, 3, and 9, including breakages, fragile X, hypo- and hyper-diploidy, breaks exchange, translocations, and ring chromosomes.

[Mohammed FM. Chromosomal abnormalities in Fanconi anaemia. Kuwait Med J. 1994; 26(1):43-7.]

Morocco

Tamary et al. (2000) studied an Iraqi-Jewish Fanconi anemia patient. They could not identify any mutations in the two FANCA alleles of this patient.

[See also: Morocco > Tamary et al., 2000].

Oman

Kannan et al. (2003) reported a case of pancytopenia which was confirmed by an aplastic bone marrow on biopsy. The presence of a rudimentary thumb on the right hand with its absence on the left hand raised the suspicion of Fanconi anemia, which was confirmed by stress induced chromosome fragility test on peripheral blood lymphocytes. He received an allogenic bone marrow transplant and his blood counts improved.

Palestine

Tamary et al. (2004) described the genotype (FANCA and FANCG) and phenotype of three consanguineous families with nine FA patients and one additional unrelated patient, all of Arab origin. Tamary et al. (2004) identified three novel disease-causing mutations: FANCA gross deletion of exons 6-31; FANCA splice-site mutation IVS 42-2A>C; and FANCG splice-site mutation IVS4+3A>G. Of the four patients from the first family with the FANCA deletion of exons 6-31, three had malformations (microcephaly, Klippel-feil disease) and developed bone marrow failure at a median age of 10.75 yr. One developed acute myelobalstic leukemia and two died of bone marrow transplantation (BMT) complications. The three patients from the second family with FANCA IVS42-2A>C had several malformations (hypoplastic thumbs, left pelvic kidney with reflux, absent left kidney, deafness, microcephaly, mental retardation). All developed bone marrow failure at an early age (median age=8.5 yr), and two developed squamous cell carcinoma at the ages of 26 and 30 yr. Two patients from the third family with FANCG IVS4+3A>G were available for evaluation. One patient had malformations (rotated left kidney, hypoplastic thumbs), and both patients developed bone marrow failure at age 12-13 yr and are currently well at age 18-21 yr (the 21 years old patient post-BMT). The clinical condition of eight patients with FANCA mutations was found severe. Tamary et al. (2004) concluded that further analysis of FA mutations and genotype-phenotype correlations may facilitate prenatal diagnosis of FA and allow for a more rational therapeutic approach, including frequent monitoring, early bone marrow transplantation, and eventually gene therapy.

Saudi Arabia

In the year 2000, Habib et al. reported a 4-year-old boy from Saudi Arabia with an established diagnosis of Fanconi anemia. Ultrasonography and a renal nuclide scan showed a solitary kidney on the left side a micturating cystourethrogram showed gross vesicoureteral reflux. The findings observed in the patient are consistent with a diagnosis of solitary crossed renal ectopia (SCRE). In addition, the patient had hypospadias and unilateral undescended testis with absent vas deferens.

Al-Hwiesh et al. (2005) reported two Saudi brothers with Fanconi Syndrome in comorbidity with familial tuberous sclerosis. In both cases, there were histories of failure to thrive and mental retardation associated with hypokalemic metabolic acidosis.

Tunisia

Bouchlaka et al. (2003) investigated FANCA ANEMIA gene mutations in 49 patients from different regions in Tunisia. Nearly, 96% of the patients presented mainly with skeletal malformations while 92% presented abnormal skin pigmentations. In 43% of the cases, profound aplastic anemia had developed. The families were mostly consanguineous 60% of which were first cousins and 25% second cousins.

[See also: Morocco > Tamary et al., 2000].

United Arab Emirates

Revesz et al. (1993) reviewed the occurrence of rare congenital forms of aplastic anemias in the United Arab Emirates. They concluded that Fanconi anemia is the most frequently diagnosed form of aplastic anemias in the UAE population.

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