Screening of a Novel Synonymous DNAH5 Variant in Histopathologically Confirmed Adenomyosis Cases from Turkiye

Berivan Guzelbag, Sevcan Aydın, Nimet Eser Ma, Nura Fitnat Topbaş Selçuki, Engin Oral, Feyza Nur Tuncer
In: Biomedicines · 2026 · vol. 14(7) , pp. 1435 · doi:10.3390/biomedicines14071435 · W7165775999
article OA: gold CC0
🔓 Open OA copy View on OpenAlex View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-26 ⓘ

This study found a novel synonymous DNAH5 variant present in 52.1% of Turkish adenomyosis patients but absent in population databases, suggesting a potential association requiring further investigation.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Background/Objectives: Adenomyosis is a common estrogen-dependent gynecological condition with a largely undefined genetic architecture. Ciliary dysfunction has been implicated in its pathogenesis, positioning genes governing ciliary structure and motility as biologically plausible candidates for investigation. The DNAH5 gene encodes a critical component of the outer dynein arms within the ciliary axoneme, and pathogenic variants are among the most common causes of primary ciliary dyskinesia. This study aimed to systematically determine the frequency of a novel synonymous DNAH5 variant, NM_001369.3:c.9258C>T, p.(Leu3086=), in a large, histopathologically confirmed sporadic adenomyosis cohort from Turkiye, and to evaluate its occurrence relative to population-level reference data. Methods: A total of 121 women with histopathologically confirmed adenomyosis following hysterectomy were enrolled. Sanger sequencing was performed under stringent quality control conditions, including primer specificity verification by NCBI BLAST and UCSC In Silico PCR. Variant frequency was compared against gnomAD v4.0 and an in-house Turkish exome database (NGS Cloud; ~30,000 sequences) using Fisher’s exact test. In silico splice site analysis was performed using SpliceAI, and variant classification followed ACMG/AMP guidelines. Results: The variant was detected in 63 of 121 patients (52.1%; 95% CI: 43.1–61.0%), exclusively in the heterozygous state; no homozygous carriers were identified. The variant was absent from both gnomAD v4.0 across all populations and the NGS Cloud Turkish exome database (MAF: 0.0000), yielding a frequency difference (p < 2.2 × 10−16). SpliceAI analysis predicted no significant splice site impact (all delta scores < 0.1). The variant was classified as a variant of uncertain significance (VUS; BP7, PM2_supporting). Conclusions: This study identifies a difference in the frequency of a novel synonymous DNAH5 variant between a histopathologically confirmed adenomyosis cohort from Turkiye and population-level reference datasets, in which the variant was absent. Given the unphenotyped nature of the reference dataset, these findings are hypothesis-generating and do not establish a causal genetic association. Replication in independent cohorts and functional studies are warranted to elucidate the biological significance of this variant in adenomyosis susceptibility.

My notes (saved in your browser only)

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (31)

Source provenance

openalex
last seen: 2026-06-27T06:06:59.084400+00:00
License: CC0 · commercial use OK