From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia

Csilla Krausz, Antoni Riera-Escamilla, Chiara Chianese, Daniel Moreno-Mendoza, Elisabet Ars, Osvaldo Rajmil, Roser Pujol, Massimo Bogliolo, Ignacio Blanco, Ines Rodríguez, Isabel Badell, Eduard Ruiz-Castañé, Jordi Surrallés

Research output: Contribution to journalArticleResearch

34 Citations (Scopus)


© 2018, American College of Medical Genetics and Genomics. 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.
Original languageEnglish
Pages (from-to)189-194
JournalGenetics in Medicine
Publication statusPublished - 1 Jan 2019


  • Azoospermia
  • Exome sequencing
  • Fanconi anemia
  • Genetics
  • Male infertility


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