Cytogenetic Assessment of Fanconi Anemia in Children With Aplastic Anemia in Tunisia

Talmoudi, Faten; Kammoun, L.; Benhalim, Nizar; Torjemane, Lamia; Ouederni, Monia; Aissaouï, Lamia; Lakhal, Amel; Mellouli, Fethi; Othmen, Tarek Ben; Béjaoui, Mohamed; Abdelhak, Sonia; Meddeb, Mounira; Dellagi, Koussay; Hdiji, Sondes; Amouri, Ahlem

doi:10.1097/mph.0b013e31827e56cb

Cited by 3 publications

(3 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results at the clinical and cytogenetic level showed the absence of any correlation between the severity of the disease and the level of cellular sensitivity to MMC which fits with the observations reported in the literature (Castella et al, 2011;Zen et al, 2011;Talmoudi et al, 2013). Therefore, the cytogenetic approach can be considered as an important diagnostic tool for aplastic anemia, especially for asymptomatic cases for whom absence of clinical signs and any familial history would made the clinical diagnosis very challenging, hence showing the importance of chromosomal breakage assessment for the establishment of an accurate and rapid diagnosis.…”

Section: Discussionsupporting

confidence: 92%

“…A total of 87 families with 113 FA patients have been addressed to our department in Institut Pasteur de Tunis (IPT) for confirmation of FA based on the standard test involving MMC-induced chromosomal breakage analysis. The cytogenetic and molecular status of 30 families with 46 patients have been previously described (Talmoudi et al, 2013;Amouri et al, 2014). Since FA is a rare disease, it was difficult to recruit a large number of patients.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

FANCA Gene Mutations in North African Fanconi Anemia Patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

Populations in North Africa (NA) are characterized by a high rate of consanguinity. Consequently, the proportion of founder mutations might be higher than expected and could be a major cause for the high prevalence of recessive genetic disorders like Fanconi anemia (FA). We report clinical, cytogenetic, and molecular characterization of FANCA in 29 North African FA patients from Tunisia, Libya, and Algeria. Cytogenetic tests revealed high rates of spontaneous chromosome breakages for all patients except two of them. FANCA molecular analysis was performed using three different molecular approaches which allowed us to identify causal mutations as homozygous or compound heterozygous forms. It included a nonsense mutation (c.2749C > T; p.Arg917Ter), one reported missense mutation (c.1304G > A; p.Arg435His), a novel missense variant (c.1258G > A; p.Asp409Glu), and the FANCA most common reported mutation (c.3788_3790delTCT; p.Phe1263del). Furthermore, three founder mutations were identified in 86.7% of the 22 Tunisian patients: (1) a deletion of exon 15, in 36.4% patients (8/22); (2), a deletion of exons 4 and 5 in 23% (5/22) and (3) an intronic mutation c.2222 + 166G > A, in 27.3% (6/22). Despite the relatively small number of patients studied, our results depict the mutational landscape of FA among NA populations and it should be taken into consideration for appropriate genetic counseling.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

FANCA Gene Mutations in North African Fanconi Anemia Patients

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the study of Talmoudi et al, 22.22% (38 patients) were diagnosed as affected with FA and 77.17% (132 patients) as unaffected according to their sensitivity to MMC. 25 By contrast, in our work using the same concentration of MMC (50 ng/mL) only 3.6% of the patients were confirmed to be FA positive and 96.4% were not.…”

Section: Discussioncontrasting

confidence: 70%

Chromosomal breakage tests in the differential diagnosis of Fanconi anemia and aplastic anemia

Farkas

Székely

Goda³

et al. 2023

European J of Haematology

View full text Add to dashboard Cite

Background: FA patients are hypersensitive to preconditioning of bone marrow transplantation.Objective: Assessment of the power of mitomycin C (MMC) test to assign FA patients. Methods:We analysed 195 patients with hematological disorders using spontaneous and two types of chromosomal breakage tests (MMC and bleomycin). In case of presumed Ataxia telangiectasia (AT), patients' blood was irradiated in vitro to determine the radiosensitivity of the patients.Results: Seven patients were diagnosed as having FA. The number of spontaneous chromosomal aberrations was significantly higher in FA patients than in aplastic anemia (AA) patients including chromatid breaks, exchanges, total aberrations, aberrant cells. MMC-induced ≥10 break/cell was 83.9 ± 11.4% in FA patients and 1.94 ± 0.41% in AA patients (p < .0001). The difference in bleomycin-induced breaks/cell was also significant: 2.01 ± 0.25 (FA) versus 1.30 ± 0.10 (AA) (p = .019). Seven patients showed increased radiation sensitivity.Both dicentric + ring, and total aberrations were significantly higher at 3 and 6 Gy compared to controls.Conclusions: MMC and Bleomycin tests together proved to be more informative than MMC test alone for the diagnostic classification of AA patients, while in vitro irradiation tests could help detect radiosensitive-as such, individuals with AT.

show abstract

Is Tunisia ready for precision medicine? Challenges of medical genomics within a LMIC healthcare system

Trabelsi,

Othman,

Bedhioufi

et al. 2024

J Community Genet

View full text Add to dashboard Cite

Cytogenetic Assessment of Fanconi Anemia in Children With Aplastic Anemia in Tunisia

Abstract: FA is an important cause of AA in Tunisia. Our report is the first study in North Africa that explored cytogenetic and phenotypic findings in FA children. It also showed the importance of mitomycin C sensitivity screening in all FA siblings.

Cited by 3 publications

References 7 publications

FANCA Gene Mutations in North African Fanconi Anemia Patients

FANCA Gene Mutations in North African Fanconi Anemia Patients

Chromosomal breakage tests in the differential diagnosis of Fanconi anemia and aplastic anemia

Is Tunisia ready for precision medicine? Challenges of medical genomics within a LMIC healthcare system

Contact Info

Product

Resources

About