• PMID: 29904161
• Gene Name: FANCA
• Condition: Sertoli cell-only syndrome (SCOS), Azoospermia
• Association: Associated
• Mutation: c.2639C>T (p.Arg880Gln), c.3788_3790delTCT (p.Phe1263del), c.3913C>T (p.Leu1305Phe), c.3913C>T (p.Leu1305Phe)
• Population size: 30
• Population details: 30 cases
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS
• Other associated phenotypes: Fanconi anemia (FA)

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

Krausz C, Riera-Escamilla A, Chianese C, Moreno-Mendoza D, Ars E, Rajmil O, Pujol R, Bogliolo M, Blanco I, Rodríguez I, Badell I, Ruiz-Castañé E, Surrallés J.

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. FAU - Krausz, Csilla AU - Krausz C AD - Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Centre of Excellence DeNothe, University of Florence, Florence, Italy. csilla.krausz@unifi.it. AD - Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Catalonia, Spain. csilla.krausz@unifi.it. FAU - Riera-Escamilla, Antoni AU - Riera-Escamilla A AD - Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Catalonia, Spain. FAU - Chianese, Chiara AU - Chianese C AD - Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Catalonia, Spain. FAU - Moreno-Mendoza, Daniel AU - Moreno-Mendoza D AD - Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Catalonia, Spain. FAU - Ars, Elisabet AU - Ars E AD - Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Catalonia, Spain. FAU - Rajmil, Osvaldo AU - Rajmil O AD - Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Catalonia, Spain. FAU - Pujol, Roser AU - Pujol R AD - Genetics Department and Biomedical Research Institute, Hospital de Sant Pau, Center for Biomedical Research on Rare Diseases (CIBERER), and Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain. FAU - Bogliolo, Massimo AU - Bogliolo M AD - Genetics Department and Biomedical Research Institute, Hospital de Sant Pau, Center for Biomedical Research on Rare Diseases (CIBERER), and Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain. FAU - Blanco, Ignacio AU - Blanco I AD - Hospital Germans Trias i Pujol, Badalona, Catalonia, Spain. FAU - Rodríguez, Ines AU - Rodríguez I AD - Hospital Germans Trias i Pujol, Badalona, Catalonia, Spain. FAU - Badell, Isabel AU - Badell I AD - Pediatrics Department, Hospital de Sant Pau, Barcelona, Catalonia, Spain. FAU - Ruiz-Castañé, Eduard AU - Ruiz-Castañé E AD - Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Barcelona, Catalonia, Spain.