Alternative titles; symbols
HGNC Approved Gene Symbol: FIGLA
Cytogenetic location: 2p13.3 Genomic coordinates (GRCh38) : 2:70,777,310-70,790,643 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p13.3 | Premature ovarian failure 6 | 612310 | Autosomal dominant; Autosomal recessive | 3 |
The mouse basic helix-loop-helix transcription factor Figla is required for normal folliculogenesis. By searching sequence databases using mouse Figla as probe, Huntriss et al. (2002) identified human FIGLA. The predicted FIGLA protein contains 186 amino acids and shares 68% identity with mouse Figla and 25% identity with a putative medaka homolog. The basic helix-loop-helix region of FIGLA shares 96% and 57% identity with those of mouse and medaka Figla, respectively. RT-PCR showed expression of FIGLA in all ovarian follicular stages and in mature oocytes, with less frequent expression in preimplantation embryos. RT-PCR of multiple tissue samples detected FIGLA expression only in primordial follicles.
Huntriss et al. (2002) determined that the FIGLA gene contains 4 exons and spans 13.3 kb.
Using genomic sequence analysis, Huntriss et al. (2002) mapped the FIGLA gene to chromosome 2p12.
Premature Ovarian Failure 6, Autosomal Dominant
Zhao et al. (2008) analyzed the FIGLA gene in 100 Chinese women with premature ovarian failure (see POF6, 612310) and identified a 22-bp deletion (608697.0001) and a 3-bp in-frame deletion (608697.0002) in 2 patients, respectively, that were not found in 304 female controls.
Premature Ovarian Failure 6, Autosomal Recessive
In 2 Chinese sisters who had premature ovarian failure-6 with primary amenorrhea, Chen et al. (2018) identified homozygosity for a c.2T-C mutation in the start codon of the FIGLA gene (608697.0003) that segregated with disease in the family and was not found in public variant databases. The authors noted that the previously reported patients with heterozygous mutations in FIGLA had secondary amenorrhea, and suggested that FIGLA haploinsufficiency may cause milder POF than homozygous mutations.
In 2 Chinese sisters with POF6 with primary amenorrhea, Yuan et al. (2019) identified homozygosity for the c.2T-C mutation in the FIGLA gene, which segregated with disease in the family and was not found in 382 unrelated Chinese controls or in 39 additional patients with POF. The authors noted that the proband's heterozygous mother was unaffected by haploinsufficiency of FIGLA.
Hu et al. (2010) found that knockdown of Figla in mice resulted in expression of testis-specific genes in ovary. Transgenic male mice engineered to express Figla in testis appeared normal at birth, grew to adulthood, and were initially fertile. However, they developed sterility by 5 months of age, with reduced testicular size, abnormalities in sperm architecture and activity, increasing vacuolization of seminiferous tubules, arrest in meiosis I, and progressive repression of testis-specific genes. Hu et al. (2010) concluded that FIGLA expression in ovary is involved in activating genes required for oogenesis and repressing genes required for spermatogenesis.
In a 36-year-old Chinese woman (proband S13) with premature ovarian failure (POF6; 612310), Zhao et al. (2008) identified heterozygosity for a 22-bp deletion in exon 1 of the FIGLA gene, causing a frameshift and premature termination of the protein, resulting in effective haploinsufficiency. The mutation was inherited from her father, who had no evident somatic anomalies; her mother and daughter did not carry the mutation and had no reproductive or menstrual dysfunction. The mutation was not found in 304 female controls with regular menstrual cycles and no history of infertility.
In a 29-year-old Chinese woman (proband S69) with premature ovarian failure (POF6; 612310), Zhao et al. (2008) identified heterozygosity for a 3-bp deletion in exon 3 of the FIGLA gene, resulting in the loss of asp140 (140delN). The mutation was not found in 304 female controls with regular menstrual cycles and no history of infertility. Yeast 2-hybrid assay demonstrated that 140delN disrupted FIGLA binding to the TCF3 (147141) helix-loop-helix domain.
In 2 Chinese sisters who had premature ovarian failure with primary amenorrhea (POF6; 612310), Chen et al. (2018) identified homozygosity for a c.2T-C transition (c.2T-C, NM_001004311) in exon 1 of the FIGLA gene, predicted to cause loss of the start codon and thus alter the open reading frame. Their first-cousin parents were heterozygous for the mutation, which was not found in the ExAC, gnomAD, 1000 Genomes Project, or dbSNP databases.
In 2 Chinese sisters with POF6 with primary amenorrhea, Yuan et al. (2019) identified homozygosity for the c.2T-C mutation in the FIGLA gene, which segregated with disease in the family and was not found in 382 unrelated Chinese controls or in 39 additional patients with POF. Functional analysis in HEK293T cells showed that transcription levels in the mutant were similar to those in wildtype, but no full-length protein was synthesized from mutant coding sequences.
Chen, B., Li, L., Wang, J., Li, T., Pan, H., Liu, B., Zhou, Y. Cao, Y., Wang, B. Consanguineous familial study revealed biallelic FIGLA mutation associated with premature ovarian insufficiency. J. Ovarian Res. 11: 48, 2018. Note: Electronic Article. [PubMed: 29914564] [Full Text: https://doi.org/10.1186/s13048-018-0413-0]
Hu, W., Gauthier, L., Baibakov, B., Jimenez-Movilla, M., Dean, J. FIGLA, a basic helix-loop-helix transcription factor, balances sexually dimorphic gene expression in postnatal oocytes. Molec. Cell. Biol. 30: 3661-3671, 2010. [PubMed: 20479125] [Full Text: https://doi.org/10.1128/MCB.00201-10]
Huntriss, J., Gosden, R., Hinkins, M., Oliver, B., Miller, D., Rutherford, A. J., Picton, H. M. Isolation, characterization and expression of the human Factor In the Germline alpha (FIGLA) gene in ovarian follicles and oocytes. Molec. Hum. Reprod. 8: 1087-1095, 2002. [PubMed: 12468641] [Full Text: https://doi.org/10.1093/molehr/8.12.1087]
Yuan, P., He, Z., Sun, S., Li, Y., Wang, W., Liang, X., Xie, X., Jiang, Y., Yang, D. Bi-allelic recessive loss-of-function mutations in FIGLA cause premature ovarian insufficiency with short stature. Clin. Genet. 95: 409-414, 2019. [PubMed: 30474133] [Full Text: https://doi.org/10.1111/cge.13486]
Zhao, H., Chen, Z.-J., Qin, Y., Shi, Y., Wang, S., Choi, Y., Simpson, J. L., Rajkovic, A. Transcription factor FIGLA is mutated in patients with premature ovarian failure. Am. J. Hum. Genet. 82: 1342-1348, 2008. [PubMed: 18499083] [Full Text: https://doi.org/10.1016/j.ajhg.2008.04.018]