From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia
Por:
Krausz, C, Riera-Escamilla, A, Chianese, C, Moreno-Mendoza, D, Ars, E, Rajmil, O, Pujol, R, Bogliolo, M, Blanco, I, Rodriguez, I, Badell, I, Ruiz-Castane, E, Surralles, J
Publicada:
1 ene 2019
Resumen:
Purpose: In about 10% of patients affected by Fanconi anemia (FA) the diagnosis is delayed until adulthood, and the presenting symptom in these "occult" FA cases is often a solid cancer and cancer treatment-related toxicity. Highly predictive clinical parameter( s) for diagnosing such an adult-onset cases are missing.
Methods: (1) Exome sequencing (ES), (2) Sanger sequencing of FANCA, (3) diepoxybutane (DEB)-induced chromosome breakage test.
Results: ES identified a pathogenic homozygous FANCA variant in a patient affected by Sertoli cell-only syndrome (SCOS) and in his azoospermic brother. Although they had no overt anemia, chromosomal breakage test revealed a reverse somatic mosaicism in the former and a typical FA picture in the latter. In 27 selected SCOS cases, 1 additional patient showing compound heterozygous pathogenic FANCA variants was identified with positive chromosomal breakage test.
Conclusion: We report an extraordinarily high frequency of FA in a specific subgroup of azoospermic patients (7.1%). The screening for FANCA pathogenic variants in such patients has the potential to identify undiagnosed FA before the appearance of other severe clinical manifestations of the disease. The definition of this high-risk group for "occult" FA, based on specific testis phenotype with mild/borderline hematological alterations, is of unforeseen clinical relevance.
Filiaciones:
Krausz, C:
Univ Florence, Ctr Excellence DeNothe, Dept Expt & Clin Biomed Sci Mario Serio, Florence, Italy
Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau IIB St Pau, Fundacio Puigvert, Androl Dept, Barcelona, Catalonia, Spain
Riera-Escamilla, A:
Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau IIB St Pau, Fundacio Puigvert, Androl Dept, Barcelona, Catalonia, Spain
Chianese, C:
Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau IIB St Pau, Fundacio Puigvert, Androl Dept, Barcelona, Catalonia, Spain
Moreno-Mendoza, D:
Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau IIB St Pau, Fundacio Puigvert, Androl Dept, Barcelona, Catalonia, Spain
Ars, E:
Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau IIB St Pau, Fundacio Puigvert, Androl Dept, Barcelona, Catalonia, Spain
Rajmil, O:
Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau IIB St Pau, Fundacio Puigvert, Androl Dept, Barcelona, Catalonia, Spain
Pujol, R:
Univ Autonoma Barcelona, Hosp St Pau, Ctr Biomed Res Rare Dis CIBERER, Genet Dept, Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Hosp St Pau, Ctr Biomed Res Rare Dis CIBERER, Biomed Res Inst, Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Catalonia, Spain
Bogliolo, M:
Univ Autonoma Barcelona, Hosp St Pau, Ctr Biomed Res Rare Dis CIBERER, Genet Dept, Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Hosp St Pau, Ctr Biomed Res Rare Dis CIBERER, Biomed Res Inst, Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Catalonia, Spain
Blanco, I:
Hosp Badalona Germans Trias & Pujol, Badalona, Catalonia, Spain
Rodriguez, I:
Hosp Badalona Germans Trias & Pujol, Badalona, Catalonia, Spain
Badell, I:
Hosp Santa Creu & Sant Pau, Pediat Dept, Barcelona, Catalonia, Spain
Ruiz-Castane, E:
Univ Autonoma Barcelona, Inst Invest Biomed Sant Pau IIB St Pau, Fundacio Puigvert, Androl Dept, Barcelona, Catalonia, Spain
Surralles, J:
Univ Autonoma Barcelona, Hosp St Pau, Ctr Biomed Res Rare Dis CIBERER, Genet Dept, Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Hosp St Pau, Ctr Biomed Res Rare Dis CIBERER, Biomed Res Inst, Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Catalonia, Spain
Green Published, Bronze
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