Heterozygous KRT32 variant is responsible for autosomal dominant loose anagen hair syndrome
Melo, M. M.; Phillippi, E.; Moninger, T.; Foxx, K.; Darbro, B.; Messingham, K. N.; Sander, E. A.; El-Shanti, H.
Show abstract
Loose Anagen Hair Syndrome is a form of non-scarring alopecia marked by easily and painlessly pluckable terminal hair during its active growth - anagen - phase. This condition is believed to result from poor hair shaft anchoring within the follicle due to premature keratinization. Our research identified the likely pathogenic c.296C>T (p.T99I) variant in KRT32, which was found to co-segregate with the disorder in a large family with autosomal dominant loose anagen hair syndrome. This study aimed to explore the role of KRT32, previously unassociated with loose anagen hair, in hair anchorage and assess the functional impact of the p.T99I variant. We hypothesized that the p.T99I variant reduces KRT32s binding affinity to KRT82, disrupting the intermediate filament structure in the hair shaft cuticle and leading to weak anagen hair anchorage. To test this hypothesis, we conducted a protein-protein interaction assay using far western blotting and performed in silico intermediate filament network segmentation analysis on high-resolution fluorescent microscopy images. Our results revealed a decreased binding affinity of KRT32T99I for KRT82 compared to KRT32WT, along with significant differences in segment count and filament brightness (thickness) between the two groups.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Glutamic acid promotes hair growth in mice 93%
- Tagging allows faithful tracing of expression and enhances biochemical detection of Ran Binding Protein 9 in vivo and reveals its interaction with Nucleolin. 93%
- Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle 92%
Similar papers in this journal
- The muscarinic acetylcholine receptor in dermal papilla cells regulates hair growth 93%
- Validation of six commercial antibodies for detection of heterologous and endogenous TRPM8 ion channel expression 91%
- A proximity complementation assay to identify small molecules that enhance the traffic of ABCA4 misfolding variants. 91%
Similar papers in this journal
- NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss 92%
- Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome 92%
- Spinocerebellar Ataxia Type 1 protein Ataxin-1 is signalled to DNA damage by Ataxia Telangiectasia Mutated kinase 91%
Similar papers in this journal
- Unsuspected consequences of synonymous and missense variants in OCA2 can be detected in blood cell RNA samples of patients with albinism 91%
- Reconstructed human pigmented skin/epidermis models achieve epidermal pigmentation through melanocore transfer. 91%
- CPT1B-Mediated Fatty Acid Oxidation Induces Pigmentation in Solar Lentigo 90%
Similar papers in this journal
- Disrupted Cholesterol Biosynthesis and Hair Follicle Stem Cell Impairment in the Onset of Alopecia 93%
- Laminin N-terminus α31 protein distribution in adult human tissues 93%
- KCa3.1-transgene induction in murine skin produces pruritic eczematous dermatitis with severe epidermal hyperplasia and hyperkeratosis 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.