Table 3.
Supportive Information from Literature and Databases for the Relevance of FANCM Variants in Infertility
| FANCM Function32 |
| interstrand cross-link removal, anti-crossover function in mitotic cells |
| replication fork repair by catalyzing fork regression |
| regulation of meiotic crossovers in D. melanogaster, A. thaliana, and S. cerevisiae |
| FANCM Expression in Human |
| GTEx, HPA: Testis enhanced (RNA tissue category) |
| protein present in the nuclei of oogonia, stronger in pachytene stage oocytes in human fetal ovaries37 |
| FANCM Expression Data in Mouse36 |
| Fancm mRNA expression levels in testicular germ cells increase through all the post-natal development and maintain high during adulthood |
| Fancm protein localizes in the cytoplasm of Sertoli cells, the cytoplasm, and Golgi of spermatogonia through to early pachytene spermatocytes, immunostaining faint or absent beyond pachytene spermatocytes |
| FANCM-Deficient Male Micea(MGI)45 |
| Abnormal spermatogonia and seminiferous tubule morphology |
| Azoospermia; some seminiferous tubules lack spermatogonia and contain no sperm |
| Small testes, hypogonadism, Leydig cell hyperplasia |
| Elevated mitotic sister chromatid exchange |
| Reduced overall and tumor-free survival |
| FANCM-Mutant Male Miceb,42 |
| Near Sertoli cell-only-like phenotype in many tubules |
| Reduced germ cells in neonates and progressive loss of germ cells in adult males |
| Elevated level of meiotic DNA damage and spontaneous sister chromatid exchange |
| Reduced testis size |
| Premature senescence and increased tumor susceptibility |
| FANCM-Mutant Female Mice (MGI)45, 46 |
| Abnormal ovary morphology |
| Depletion of primordial follicles and decreased mature ovarian follicle number |
| Transmission ratio distortion: fewer than expected females |
| Reduced overall and tumor-free survival |
| FANCM Loss-of-Function Mutation in Females37 |
| irregular cycles, hot flashes, spaniomenorrhea |
| high FSH and low AMH levels |
| primary ovarian insufficiency |
Abbreviations: GTEx, The Genotype-Tissue Expression; HPA, The Human Protein Atlas; MGI, Mouse Genome Informatics; FSH, follicle-stimulating hormone; AMH, anti-müllerian hormone.
a
Homozygous deletion of exon 2, leading to frameshift and premature stop in exon 3.
b
Homozygous p.Cys142Arg mutation in conserved DEXDc domain.