Journal article
Heterozygous KRT32 variant is responsible for autosomal dominant loose anagen hair syndrome
HGG advances, Vol.6(4), 100495
10/2025
DOI: 10.1016/j.xhgg.2025.100495
PMCID: PMC12409965
PMID: 40814173
Abstract
Loose Anagen Hair Syndrome is a form of childhood-onset non-scarring alopecia marked by easily and painlessly pluckable terminal hair during its active growth - anagen - phase and believed to result from poor hair shaft anchoring within the follicle due to premature keratinization. Our study identified a plausibly pathogenic variant in KRT32 (c.296C>T; p.Thr99Ile) that co-segregates with the phenotype in a large family. This study aimed to explore the role of KRT32, previously unassociated with loose anagen hair, in hair anchorage and assess the functional impact of its p.Thr99Ile variant. We hypothesized that the p.Thr99Ile variant reduces the binding affinity of KRT32 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 showed a decreased binding affinity of KRT32
to KRT82 when compared to KRT32
. There were significant differences in segment count and filament thickness, as measured by brightness, between the KRT32
and the KRT32
. We conclude that the c.296C>T variant of KRT32 is associated with loose anagen hair phenotype.
Details
- Title: Subtitle
- Heterozygous KRT32 variant is responsible for autosomal dominant loose anagen hair syndrome
- Creators
- Marcelo Melo - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAElizabeth Phillippi - University of IowaThomas Moninger - University of IowaLisa J Stille - University of IowaKya Foxx - University of IowaBenjamin Darbro - University of IowaKelly N Messingham - University of Iowa, DermatologyEdward A Sander - University of IowaHatem El-Shanti - University of Iowa
- Resource Type
- Journal article
- Publication Details
- HGG advances, Vol.6(4), 100495
- DOI
- 10.1016/j.xhgg.2025.100495
- PMID
- 40814173
- PMCID
- PMC12409965
- NLM abbreviation
- HGG Adv
- ISSN
- 2666-2477
- eISSN
- 2666-2477
- Publisher
- CELL PRESS
- Grant note
- University of Iowa Carver College of MedicineUniversity of Iowa Stead Family Children's Hospital
The authors wish to thank the family members for their participa-tion in the study, H. Major and the staff of the Shivanand R. Patil Molecular and Cytogenetics Laboratory at the University of Iowa for their help in variant identification and annotation, and M. Schultz and X. Bing for their laboratory technical support. The data presented herein were obtained at the Genomics Division of the Iowa Institute of Human Genetics, which is supported in part by the University of Iowa Carver College of Medicine. This research received no external funding; it was supported by multiple internal grants and start-up and discretionary funds from the University of Iowa Stead Family Children's Hospital.
- Language
- English
- Electronic publication date
- 08/14/2025
- Date published
- 10/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Dermatology; Stead Family Department of Pediatrics; Orthopedics and Rehabilitation; Medical Genetics and Genomics; Craniofacial Anomalies Research Center; Chemical and Biochemical Engineering
- Record Identifier
- 9984946847202771
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