Cytogenetic findings in Polish patients with suspected Fanconi anemia.

Fanconi anemia chromosome breakage test mitomycin C

Journal

Advances in clinical and experimental medicine : official organ Wroclaw Medical University
ISSN: 1899-5276
Titre abrégé: Adv Clin Exp Med
Pays: Poland
ID NLM: 101138582

Informations de publication

Date de publication:
04 Aug 2023
Historique:
received: 12 02 2023
revised: 06 04 2023
accepted: 26 06 2023
medline: 4 8 2023
pubmed: 4 8 2023
entrez: 4 8 2023
Statut: aheadofprint

Résumé

The high sensitivity of cells of Fanconi anemia (FA) patients to DNA cross-linking agents (clastogens), such as mitomycin C (MMC), was used as a screening tool in Polish children with clinical suspicion of FA. The aim of the study was to compare chromosome fragility between 3 groups, namely non-FA, possible mosaic FA and FA patients. The study included 100 children with hematological manifestations and/or congenital defects characteristic of FA, and 100 healthy controls. Blood samples obtained from participants were analyzed using an MMC-induced chromosomal breakage test. Patients with clinical suspicion of FA were divided into 3 subgroups based on the MMC test results, namely FA, possible mosaic FA and non-FA. Thirteen out of 100 patients had a true FA cellular phenotype. The mean value of MMC-induced chromosome breaks/cell for FA patients was higher than for non-FA patients (6.67 ±3.92 compared to 0.23 ±0.18). In addition, the percentage of cells with spontaneous aberrations was more than 9 times higher in FA patients than in non-FA patients. Our results confirmed that the MMC sensitivity test distinguishes between individuals affected by FA, those with possible somatic mosaicism, and patients with bone marrow failure for other reasons, who were classified as non-FA in the first diagnostic step. However, a definitive differential diagnosis requires follow-up mutation testing and chromosome breakage analysis of skin fibroblasts.

Sections du résumé

BACKGROUND BACKGROUND
The high sensitivity of cells of Fanconi anemia (FA) patients to DNA cross-linking agents (clastogens), such as mitomycin C (MMC), was used as a screening tool in Polish children with clinical suspicion of FA.
OBJECTIVES OBJECTIVE
The aim of the study was to compare chromosome fragility between 3 groups, namely non-FA, possible mosaic FA and FA patients.
MATERIAL AND METHODS METHODS
The study included 100 children with hematological manifestations and/or congenital defects characteristic of FA, and 100 healthy controls. Blood samples obtained from participants were analyzed using an MMC-induced chromosomal breakage test.
RESULTS RESULTS
Patients with clinical suspicion of FA were divided into 3 subgroups based on the MMC test results, namely FA, possible mosaic FA and non-FA. Thirteen out of 100 patients had a true FA cellular phenotype. The mean value of MMC-induced chromosome breaks/cell for FA patients was higher than for non-FA patients (6.67 ±3.92 compared to 0.23 ±0.18). In addition, the percentage of cells with spontaneous aberrations was more than 9 times higher in FA patients than in non-FA patients.
CONCLUSIONS CONCLUSIONS
Our results confirmed that the MMC sensitivity test distinguishes between individuals affected by FA, those with possible somatic mosaicism, and patients with bone marrow failure for other reasons, who were classified as non-FA in the first diagnostic step. However, a definitive differential diagnosis requires follow-up mutation testing and chromosome breakage analysis of skin fibroblasts.

Identifiants

pubmed: 37540155
doi: 10.17219/acem/168825
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Auteurs

Anna Repczyńska (A)

Department of Clinical Genetics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.

Katarzyna Jułga (K)

Department of Clinical Genetics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.

Andżelika Lorenc (A)

Department of Biopharmacy, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.

Jolanta Skalska-Sadowska (J)

Department of Oncology, Hematology and Pediatric Transplantology, Poznan University of Medical Sciences, Poland.

Mariusz Wysocki (M)

Department of Pediatric Hematology and Oncology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.

Agnieszka Zaucha-Prażmo (A)

Department of Pediatric Haematology, Oncology and Transplantology, Medical University of Lublin, Poland.

Katarzyna Drabko (K)

Department of Pediatric Haematology, Oncology and Transplantology, Medical University of Lublin, Poland.

Artur Bossowski (A)

Department of Pediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University of Bialystok, Poland.

Bożena Dembowska-Bagińska (B)

Department of Oncology, Children's Memorial Health Institute, Warsaw, Poland.

Jacek Wachowiak (J)

Department of Oncology, Hematology and Pediatric Transplantology, Poznan University of Medical Sciences, Poland.

Adam Buciński (A)

Department of Biopharmacy, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.

Olga Haus (O)

Department of Clinical Genetics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.

Classifications MeSH