Web of Science: 1 citations, Scopus: 2 citations, Google Scholar: citations,
From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia
Krausz, Csilla (Institut d'Investigació Biomèdica Sant Pau)
Riera-Escamilla, Antoni (Institut d'Investigació Biomèdica Sant Pau)
Chianese, Chiara (Institut d'Investigació Biomèdica Sant Pau)
Moreno-Mendoza, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Ars Criach, Elisabet (Institut d'Investigació Biomèdica Sant Pau)
Rajmil, Osvaldo (Institut d'Investigació Biomèdica Sant Pau)
Pujol i Calvet, M. Roser (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Bogliolo, Massimo (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Blanco, Ignacio (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodríguez, Inés (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Badell Serra, Isabel (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública)
Ruiz-Castañé, Eduard (Institut d'Investigació Biomèdica Sant Pau)
Surrallés i Calonge, Jordi (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date: 2019
Abstract: 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.
Note: Número d'acord de subvenció EC/FP7/305421
Note: Número d'acord de subvenció EC/FP7/289880
Note: Número d'acord de subvenció MINECO/SAF2015-64152-R
Note: Número d'acord de subvenció MINECO/FIS PI17/01822
Note: Número d'acord de subvenció MINECO/FIS PI14/01250
Rights: Tots els drets reservats.
Language: Angles.
Document: article ; recerca ; publishedVersion
Subject: Azoospermia ; Exome sequencing ; Fanconi anemia ; Genetics ; Male infertility
Published in: Genetics in Medicine, Vol. 21, issue 1 (Jan. 2019) , p. 189-194, ISSN 1098-3600

DOI: 10.1038/s41436-018-0037-1


Available from: 2019-06-30
Postprint

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2018-11-01, last modified 2019-05-14



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