The causes of Fanconi anemia in South Asia and the Middle East: A case series and review of the literature

Thompson, Ashley S.; Saba, Nusrat; McReynolds, Lisa J.; Munir, Saeeda; Ahmed, Parvez; Sajjad, Sumaira; Jones, Kristine; Yeager, Meredith; Donovan, Frank X.; Chandrasekharappa, Settara C.; Alter, Blanche P.; Savage, Sharon A.; Rehman, Sadia

doi:10.1002/mgg3.1693

Cited by 4 publications

(4 citation statements)

References 67 publications

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“…The mean age group of non-FA anemia (group 1) and FA patients (group 2) was in accordance with other reports from the literature where most patients fall under the same age group (Tipping et al, 2001;Issaragrisil et al, 2006;Alter Giri, 2016;Siddiqui et al, 2020;Thompson et al, 2021).…”

Section: Cytogenetic Examinationsupporting

confidence: 90%

Fanconi and Non-Fanconi anemia: A Single Center Experience of A Large Egyptian Cohort

Thomas

Farid

El‐Kamah

et al. 2022

Middle East Journal of Medical Genetics

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Background: Bone marrow failure syndromes are a group of diseases that could be inherited as congenital or acquired aplastic anemia. Fanconi anemia (FA) is the commonest cause of congenital aplastic anemia. Aim: This study reports patients with congenital aplastic anemia aiming to reveal the clinical and cytogenetic differences between the two groups, (non-Fanconi and Fanconi anemia) also to compare between patients included in this study with those from different ethnic populations. Patients and Methods: 204 patients with aplastic anemia were included (101 non-Fanconi and 103 Fanconi). Induction of chromosomal breakage by DEB was done to all patients to confirm the diagnosis of FA and to determine the degree of chromosomal breakage. Results: Mean age of non-FA and FA patients was 10 ± 4.24 and 9 ± 4.61 years respectively with high consanguinity rate (65% 79% respectively). 24.7% of non-FA patients exhibited very severe aplastic anemia, while the majority (72.2%) exhibited severe aplastic anemia. Few patients (1.9%) had non-severe form. While, in FA patients, very severe aplastic anemia was present in 10.6%; 84.4% had severe form and 4.8 % had non-severe form. These results were significant between the two groups (p=0.02). 12.6% of FA patients showed mosaic DEB results. Comparing FA cases with one cell line and those with two cell lines regarding patients' percentiles, hematological abnormalities and degree of severity revealed no significant difference. Conclusion:This study reports a large number of Egyptian patients diagnosed as congenital aplastic anemia with relatively high number of FA patients due to higher rate of consanguinity in Egypt. FA accounts for a significant percentage of congenital aplastic anemia and should be ruled out stressing on congenital anomalies and hematologic findings. Further evaluation of patients who share similar phenotypes and genetic studies are highly recommended to identify the dominant FA types in Egypt.

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Section: Cytogenetic Examinationsupporting

confidence: 90%

Fanconi and Non-Fanconi anemia: A Single Center Experience of A Large Egyptian Cohort

Thomas

Farid

El‐Kamah

et al. 2022

Middle East Journal of Medical Genetics

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“…Currently, fewer FANCL mutation sites have been reported, and all of them are homozygous or compound heterozygous mutations in FA cases. [14][15][16][17][18][19][20] We summarize these mutation sites in Table 1.…”

Section: Discussionmentioning

confidence: 99%

“…Homozygous 12 [19] + 2 [20] 10 c.1092G > A p.Trp341_Lys364del c.592delA (intron) -Compound heterozygosity 1 [19] FA = Fanconi anemia, FANCL = FA complementation group L.…”

Section: Patient Informationmentioning

confidence: 99%

An acquired BMF with FANCL gene heterozygous mutation: Case report

Zhang¹,

Xiao²,

Miao³

et al. 2023

Medicine

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Rationale: Bone marrow failure (BMF) includes inherited and acquired BMFs. Acquired BMF can be secondary to various factors, such as autoimmune dysfunction, benzene, drugs, radiation, viral infection and so on. Fanconi anemia (FA) complementation group L (FANCL) is an E3 ubiquitin ligase that participates in the repair of DNA damage. Homozygous or compound heterozygous mutations of FANCL can lead to the onset of FA, which is one of the most common inherited BMFs.Patient concerns and Diagnoses: Here, we report a case of acquired BMF. This patient had a history of benzene exposure for half a year before the onset of the disease, and presented with progressive pancytopenia, especially the reduction of erythrocytes and megakaryocyte, without malformation. Interestingly, this patient and his brother/father had a heterozygous (non-homozygous/compound heterozygous) mutation (Exon9, c.745C > T, p.H249Y) in the FANCL gene. Interventions and Outcomes:The patient successfully underwent unrelated and fully compatible umbilical cord blood hematopoietic stem cell transplantation.Lessons subsections: We report for the first time an acquired BMF case with FANCL gene heterozygous mutation, and the mutation site (Exon9, c.745C > T, p.H249Y) has never been reported. This case suggests that heterozygous mutations in FANCL gene may be associated with increased susceptibility to acquired BMF. Based on current reports and this case, we speculate that heterozygous mutations in the FA complementation gene may exist in a certain proportion of tumor and acquired BMF patients, but have not been detected. We recommend routine screening for FA complementation gene mutations in tumor and acquired BMF patients in clinical practice. If positive results are found, further screening can be conducted on their families.

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“…In recent years, advances in Fanconi anaemia research have included discovery of novel pathogenic variants, recognition of germline mosaicism, genetic reversion identified in some tissue types, and various clinical trials for novel treatment of Fanconi anaemia and its complications [15 ▪ ,16,17]. Furthermore, differences in genotype-phenotype outcome associations present potential avenues of inquiry into tailored clinical management based on genetic testing [18 ▪ ].…”

Section: Fanconi Anaemiamentioning

confidence: 99%

Inherited bone marrow failure syndromes: a review of current practices and potential future research directions

Deng

McReynolds

2022

Current Opinion in Pediatrics

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Purpose of reviewRecent advances in diagnosis and treatment of inherited bone marrow failure syndromes (IBMFS) have significantly improved disease understanding and patient outcomes. Still, IBMFS present clinical challenges that require further progress. This review aims to provide an overview of the current state of diagnosis and treatment modalities of the major IBMFS seen in paediatrics and present areas of prioritization for future research. Recent findingsHaematopoietic cell transplantation (HCT) for IBMFS has greatly improved in recent years, shifting the research and clinical focus towards cancer predispositions and adverse effects of treatment. Each year, additional novel genes and pathogenic variants are described, and genotype-phenotype mapping becomes more sophisticated. Moreover, novel therapeutics exploring disease-specific mechanisms show promise to complement HCT and treat patients who cannot undergo current treatment options. SummaryResearch on IBMFS should have short-term and long-term goals. Immediate challenges include solidifying diagnostic and treatment guidelines, cancer detection and treatment, and continued optimization of HCT. Long-term goals should emphasize genotype-phenotype mapping, genetic screening tools and genetargeted therapy.

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The causes of Fanconi anemia in South Asia and the Middle East: A case series and review of the literature

Cited by 4 publications

References 67 publications

Fanconi and Non-Fanconi anemia: A Single Center Experience of A Large Egyptian Cohort

Fanconi and Non-Fanconi anemia: A Single Center Experience of A Large Egyptian Cohort

An acquired BMF with FANCL gene heterozygous mutation: Case report

Inherited bone marrow failure syndromes: a review of current practices and potential future research directions

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