BOD1L1 – Premature Menopause

The association between BOD1L1 and premature menopause is supported by recent observational studies that employed whole exome sequencing and rare variant burden analyses. In a large multi‐center cohort of women diagnosed with primary ovarian insufficiency (POI), defined by amenorrhea and elevated follicle‑stimulating hormone levels, BOD1L1 emerged as one of seven candidate risk genes (PMID:34718612).

Clinically, the evidence is based on candidate heterozygous rare variants identified in approximately 291 probands (PMID:34718612). Although explicit familial segregation counts are not detailed for BOD1L1, the multi‑patient study design across several international centers lends added weight to the gene‑disease association. The overall clinical validity has been appraised as Moderate given the replication across cohorts and supportive experimental data.

Genetic evidence for BOD1L1 consists of a burden of rare deleterious variants identified in POI patients. While no specific HGVS‐formatted coding variant was explicitly reported for BOD1L1 in the available evidence, the aggregate findings from case reports and multi‑patient studies underscore the importance of candidate heterozygous variants in the disease context (PMID:34718612).

The variant spectrum, although not delineated at the single‐variant level with an HGVS string for BOD1L1, reflects an enriched load of alleles that are predicted to affect gene function. This suggests that the underlying pathogenic mechanism may involve haploinsufficiency or dominant‑negative effects, consistent with the heterozygous presentation observed in POI cohorts.

Functional studies, including model organism experiments, have provided supportive evidence. Experimental assessments in Drosophila and cellular systems have replicated aspects of the POI phenotype, lending further credence to the role of BOD1L1 in ovarian function and premature menopause (PMID:30957200).

In summary, the integrated genetic and functional data indicate that BOD1L1 is a moderately supported candidate gene for premature menopause. Key take‑home: Incorporation of BOD1L1 into diagnostic and risk‑assessment panels may improve clinical decision‑making in women presenting with unexplained POI.

References

• The Journal of clinical endocrinology and metabolism | 2022 | Causal and Candidate Gene Variants in a Large Cohort of Women With Primary Ovarian Insufficiency PMID:34718612
• Journal of gastrointestinal cancer | 2020 | Whole Exome Sequencing Reveals a Novel Damaging Mutation in Human Fibroblast Activation Protein in a Family with Esophageal Squamous Cell Carcinoma PMID:30957200

Evidence Based Scoring (AI generated)