Fanconi-like anemia related to a FANCM mutation

Encarnación, J.A.; Cerezuela, Paula; Español, Ignacio; Garcia, Marta; Manso, Ana Cristina; Garrigós, Noemí; Viney, AC; Minguillón, Jordi; Surrallés, Jordi

doi:10.1016/j.ejmg.2021.104399

Cited by 6 publications

(4 citation statements)

References 11 publications

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“…FANCM mutation carriers do not develop classical Fanconi anemia; they develop Fanconi-like anemia, often without clinical symptoms [ 28 ]. However, it was shown here that mutations in FA genes, as well as in FANCM, are related to the hypersensitivity of these patients to DNA-damaging agents such as chemotherapy and radiotherapy, which might lead to poor treatment outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, the putative involvement of FANCM gene variants in male and female fertility has been described in several families. Male patients carrying biallelic mutations in FANCM exhibit sterility characterized by non-obstructive azoospermia and Sertoli cell-only syndrome [ 25 , 26 , 27 , 28 ]. Considering cancer, FANCM has also been reported to be a tumor suppressor and cancer-susceptibility gene [ 29 , 30 ], with its germline variants related to breast cancer [ 31 , 32 , 33 , 34 ] but also to some other cancers, such as B-cell precursor lymphoblastic leukemia or squamous cell carcinoma [ 28 , 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

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FANCM Gene Variants in a Male Diagnosed with Sertoli Cell-Only Syndrome and Diffuse Astrocytoma

Klarić,

Marić,

Žunić

et al. 2024

Genes

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Azoospermia is a form of male infertility characterized by a complete lack of spermatozoa in the ejaculate. Sertoli cell-only syndrome (SCOS) is the most severe form of azoospermia, where no germ cells are found in the tubules. Recently, FANCM gene variants were reported as novel genetic causes of spermatogenic failure. At the same time, FANCM variants are known to be associated with cancer predisposition. We performed whole-exome sequencing on a male patient diagnosed with SCOS and a healthy father. Two compound heterozygous missense mutations in the FANCM gene were found in the patient, both being inherited from his parents. After the infertility assessment, the patient was diagnosed with diffuse astrocytoma. Immunohistochemical analyses in the testicular and tumor tissues of the patient and adequate controls showed, for the first time, not only the existence of a cytoplasmic and not nuclear pattern of FANCM in astrocytoma but also in non-mitotic neurons. In the testicular tissue of the SCOS patient, cytoplasmic anti-FANCM staining intensity appeared lower than in the control. Our case report raises a novel possibility that the infertile carriers of FANCM gene missense variants could also be prone to cancer development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FANCM Gene Variants in a Male Diagnosed with Sertoli Cell-Only Syndrome and Diffuse Astrocytoma

Klarić,

Marić,

Žunić

et al. 2024

Genes

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“…All 12 cases reported to date of biallelic FANCM variants associated with malignancies are summarized in Table 1, including this case (number 12). [5][6][7][8][9] All cases harboured homozygous variants except Cases 6, 10 and 12, which were compound heterozygous. Seven individuals (58%) were females, and the median age of first malignancy diagnosis was 32 (28-51) years.…”

Section: Myelodysplastic Syndrome and Multiple Solid Tumours In An In...mentioning

confidence: 95%

Myelodysplastic syndrome and multiple solid tumours in an individual with compound heterozygous deleterious FANCM variants: A case report and review of the literature

Ng,

Warwick,

Craft

et al. 2023

Br J Haematol

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“…In humans and mice, FANCM is required for normal fertility and gametogenesis [5–12]. Reports of male patients with biallelic mutations in FANCM revealed sterility characterised by non-obstructive azoospermia and Sertoli cellonly seminiferous epithelium [8, 9, 13]. Females with a homozygous pathogenic FANCM mutation experienced premature ovarian insufficiency and therefore early menopause [10].…”

Section: Introductionmentioning

confidence: 99%

Fancm regulates meiotic double-strand break repair pathway choice in mammals

Tsui

Lyu

Novakovic

et al. 2022

Preprint

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Meiotic crossovers are required for accurate chromosome segregation and to produce new allelic combinations. Meiotic crossover numbers are tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. Here, we describe the tumour suppressor FANCM as a meiotic anti-crossover factor in mammals. Crossover analyses with single-gamete and pedigree datasets both reveal a genome-wide increase in crossover frequencies in Fancm-deficient mice. Gametogenesis is heavily perturbed in Fancm loss of function mice, which is consistent with the reproductive defects reported in humans with biallelic FANCM mutations. A portion of the gametogenesis defects can be attributed to the cGAS-STING pathway. Despite the gametogenesis phenotypes in Fancm mutants both sexes were capable of producing offspring. We propose that the anti-crossover function and role in gametogenesis of Fancm are separable and will inform diagnostic pathways for human genomic instability disorders.

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Fanconi-like anemia related to a FANCM mutation

Cited by 6 publications

References 11 publications

FANCM Gene Variants in a Male Diagnosed with Sertoli Cell-Only Syndrome and Diffuse Astrocytoma

FANCM Gene Variants in a Male Diagnosed with Sertoli Cell-Only Syndrome and Diffuse Astrocytoma

Myelodysplastic syndrome and multiple solid tumours in an individual with compound heterozygous deleterious FANCM variants: A case report and review of the literature

Fancm regulates meiotic double-strand break repair pathway choice in mammals

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