Mitomycin C Chromosome Stress Test to Identify Hypersensitivity to Bifunctional Alkylating Agents in Patients With Fanconi Anemia or Aplastic Anemia

Kuffel, Daniel G.; Lindor, Noralane M.; Litzow, Mark R.; Zinsmeister, Alan R.; Dewald, Gordon W.

doi:10.4065/72.6.579

Cited by 9 publications

(2 citation statements)

References 6 publications

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“…CBA was performed using a previously described protocol 31 as detailed in the online supplemental methods . A total of 40 well-spread metaphases of the cells with normal ploidy were analysed.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive laboratory diagnosis of Fanconi anaemia: comparison of cellular and molecular analysis

et al. 2023

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BackgroundFanconi 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. We performed chromosome breakage analysis (CBA), FANCD2 ubiquitination (FANCD2-Ub) analysis and exome sequencing of 142 Indian patients with FA and evaluated the efficiencies of these methods in FA diagnosis.MethodsWe performed CBA and FANCD2-Ub analysis in the blood cells and fibroblasts of patients with FA. Exome sequencing with improved bioinformatics to detect the single number variants and CNV was carried out for all the patients. Functional validation of the variants with unknown significance was done by lentiviral complementation assay.ResultsOur study showed that FANCD2-Ub analysis and CBA on peripheral blood cells could diagnose 97% and 91.5% of FA cases, respectively. Exome sequencing identified the FA genotypes consisting of 45 novel variants in 95.7% of the patients with FA.FANCA(60.2%),FANCL(19.8%) andFANCG(11.7%) were the most frequently mutated genes in the Indian population. AFANCLfounder mutation c.1092G>A; p.K364=was identified at a very high frequency (~19%) in our patients.ConclusionWe performed a comprehensive analysis of the cellular and molecular tests for the accurate diagnosis of FA. A new algorithm for rapid and cost-effective molecular diagnosis for~90% of FA cases has been established.

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Section: Methodsmentioning

confidence: 99%

Comprehensive laboratory diagnosis of Fanconi anaemia: comparison of cellular and molecular analysis

et al. 2023

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“…Collectively, these conditions are referred to as chromosome breakage syndromes. For example, the chromosomes of patients with Fanconi anemia are especially sensitive to bifunctional alkylating agents such as diepoxybutane or mitomycin C. [40][41][42] In patients with Fanconi anemia, these agents produce excessive chromosome breakage, including a specific type of chromosome anomaly called radial configurations (Figure 17).…”

Section: A B Cmentioning

confidence: 99%