KRT71 – Isolated familial woolly hair disorder

Autosomal dominant isolated familial woolly hair disorder is characterized by tightly curled, woolly scalp hair often accompanied by variable hypotrichosis. The disorder is defined by sparse, brittle hair shafts that are poorly anchored in the anagen phase, leading to hair fragility and variable expressivity. The causative gene, KRT71, encodes an inner root sheath–specific type II keratin critical for intermediate filament formation in hair follicles. The disease entry isolated familial woolly hair disorder falls under MONDO_0008686 and presents predominantly as woolly hair (HP:0002224) with hypotrichosis (HP:0002209) and variable expressivity (HP:0003828).

Genetic evidence derives from two unrelated autosomal dominant pedigrees (total ≥5 affected relatives) demonstrating co-segregation of KRT71 variants with disease ([PMID:22592156]; [PMID:40282419]). In a Japanese kindred, a heterozygous missense change c.422T>G (p.Phe141Cys) within the helix initiation motif segregated in affected members and was absent in controls ([PMID:22592156]). In a second mother–daughter pair, a heterozygous intronic variant altering tail‐domain splicing was identified and co-segregated with woolly hair and loose anagen features ([PMID:40282419]).

The variant spectrum currently includes one coding change, c.422T>G (p.Phe141Cys), which disrupts the helix initiation motif, and an intronic splicing variant that inserts 12 bases into the mature transcript. Both variants show autosomal dominant inheritance and have not been reported as population polymorphisms.

Functional studies provide concordant experimental evidence. In cultured keratinocytes, the p.Phe141Cys mutant protein disrupts intermediate filament assembly, causing cytoskeletal aggregation ([PMID:22592156]). A minigene assay confirmed that the intronic variant causes aberrant splicing in the tail domain, adding four amino acids and impairing filament biomechanics ([PMID:40282419]). These assays support a dominant‐negative mechanism.

No conflicting reports have been documented, and no functionally benign variants in KRT71 have been associated with isolated woolly hair. The collective data support a direct pathogenic role for KRT71 variants in this phenotype.

Key Take-home: Heterozygous KRT71 variants cause autosomal dominant isolated familial woolly hair disorder through dominant‐negative disruption of keratin filaments and should be included in targeted diagnostic panels.

References

• The Journal of investigative dermatology • 2012 • A missense mutation within the helix initiation motif of the keratin K71 gene underlies autosomal dominant woolly hair/hypotrichosis PMID:22592156
• Genes • 2025 • Loose Anagen Hair Associated with Wooly Hair Caused by a Heterozygous, Intronic KRT71 Variant PMID:40282419

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