Fanconi Anemia Gene Variants in Patients with Gonadal Dysfunction.
Azoospermia
Fanconi anemia
Gonadal dysfunction
Hypomorphic variants
Mosaic
Primary ovarian insufficiency
Journal
Reproductive sciences (Thousand Oaks, Calif.)
ISSN: 1933-7205
Titre abrégé: Reprod Sci
Pays: United States
ID NLM: 101291249
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
29
12
2020
accepted:
11
04
2021
pubmed:
13
5
2021
medline:
15
4
2022
entrez:
12
5
2021
Statut:
ppublish
Résumé
Fanconi anemia (FA) is a multisystem disease, characterized by the triad of physical abnormalities, bone marrow failure, and increased risk for malignancy. In the past few years, data has accumulated regarding fertility issues in FA patients, mostly due to gonadal dysfunction, which is prevalent in FA patients reaching puberty. It seems that attenuated FA phenotype lacking the classical manifestations often is presented with POI or azoospermia. Searching the literature, we summarized data regarding FA patients presenting as suffering from sub/infertility due to gonadal dysfunction, with or without other FA symptoms. We present a summary of the patients having biallelic pathogenic variants in FA genes FANCA, FANCM, BRCA2, and XRCC2 that presented with gonadal dysfunction with or without other phenotypic features of FA. Some were in mosaic, while some are considered hypomorphic, enabling residual protein function. There are also a few descriptions of POI associated with monoallelic pathogenic variants in FANCA, BRCA2, and FANCL. We conclude that the diagnosis of FA in gonadal dysfunction patients is of utmost importance due to its actionability. Follow-up strategies in FA patients are designed to discover early stages of leukemias and solid tumors and thus save lives. The feasibility of next-generation sequencing (NGS) can now ease this diagnostic procedure. An open question is the justification of performing NGS for all isolated azoospermia/POI patients.
Identifiants
pubmed: 33977503
doi: 10.1007/s43032-021-00582-7
pii: 10.1007/s43032-021-00582-7
doi:
Substances chimiques
DNA-Binding Proteins
0
XRCC2 protein, human
0
FANCM protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1408-1413Informations de copyright
© 2021. Society for Reproductive Investigation.
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