Open AccessClinical, cytogenetic and molecular findings in nine Moroccan patients with Fanconi anemia
Author(s) -
Yassamine Doubaj,
Abdelali Zrhidri,
Siham Chafai Elalaoui,
Jaber Lyahyai,
Youssef El Kadiri,
Nadia Elkassimi,
Aziza Sbiti,
Maria El Kababri,
Laïla Hessissen,
Abdelaziz Sefiani
Publication year - 2021
Publication title -
the pan african medical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.287
H-Index - 30
ISSN - 1937-8688
DOI - 10.11604/pamj.2021.39.72.27220
Subject(s) - fanca , fanconi anemia , fancd2 , medicine , genetics , mutation , proband , multiplex ligation dependent probe amplification , gene , bioinformatics , biology , dna repair , exon
Fanconi anemia (FA) is a rare inherited hematological disease due to a defect in the DNA repair pathway resulting in congenital abnormalities and high susceptibility to develop cancers. The cytogenetic analysis using alkylating agents is still a reference test to establish the diagnosis. Despite the genetic heterogeneity, the identification of the causal mutation is actually performed especially after the development of next generation sequencing (NGS). Methods we report here nine Moroccan patients referred to the department of Medical Genetics for suspicion of FA. We realized a genetic consultation to establish a clinical record with biological data before carrying out the genetic analysis. Karyotyping with mitomycin was performed for all the probands before elaborating molecular study. We used massively parallel sequencing to analyse the three most frequent mutated genes FANCA, FANCC, and FANCG, representing 84% of all genes involved in FA. Results all the patients showed hematological signs associated with at least one extra-hematological congenital anomaly. The chromosomal breaks were significantly higher for the nine patients, compared to the controls. The molecular diagnosis was confirmed in 8 of the 9 families tested (88.8%) with 4 novel mutations. The next generation based sequencing identified 9 variations: 6 in the FANCA gene (66.6%), 3 in the FANCG gene (33.3%) and no FANCC variation was found. Of those, 7 were homozygous and 2 were compounds heterozygous. Conclusion to the best of our knowledge, this is the first molecular report of Moroccan patients with FA suggesting the predominance of two genes without any recurrent mutation. The molecular analysis of FANCA and FANCG genes should be offered first for all patients in Morocco.