HEREDITARY hypotrichosis showed distinct genotype–phenotype patterns in a multicentre Chinese cohort, with causative genes associated with differences in disease onset, severity, and hair shaft morphology.
The observational study included 47 unrelated families and 107 affected individuals with clinically and genetically confirmed non-syndromic hereditary hypotrichosis (NSHH). Genetic analysis used next-generation sequencing with Sanger validation, while clinical features including age at onset, severity, hair shaft morphology, and extracranial hair involvement were systematically assessed.
Researchers identified 11 causative genes across the cohort. LIPH was the most frequently identified, occurring in 18 families (38.3%), followed by LSS in 10 families (21.27%) and HRURF in seven families (14.89%).
The cohort demonstrated substantial phenotypic heterogeneity, with genotype-dependent patterns observed across several clinical characteristics.
Congenital onset was common among individuals with LIPH, LSS, and HRURF variants. In contrast, postnatal onset was observed in individuals with APCDD1, KRT86, and HR variants.
Preliminary genotype–phenotype analysis of LIPH also suggested allele-specific effects. Variants associated with c.736T>A were linked to more severe hypotrichosis than those associated with c.742C>A.
In HRURF, two recurrently affected regions were identified. These involved the start codon and a region encoding amino acids 23–28, further supporting genotype-specific patterns within NSHH.
Based on the observed genotype–phenotype relationships, the researchers proposed a preliminary phenotype-driven candidate-gene prioritisation framework. Such an approach could assist clinicians in narrowing potential genetic causes based on clinical presentation.
The study also included an exploratory analysis of topical minoxidil, which showed variable treatment responses among affected individuals. However, the abstract did not provide specific response rates or further treatment comparisons.
Overall, the findings expand understanding of the genetic architecture of NSHH in the Chinese population and highlight relationships between specific genetic variants and clinical presentation. The proposed phenotype-driven framework may support clinical evaluation and candidate-gene prioritisation in patients with suspected hereditary hypotrichosis.
Reference
Zhao A et al. Distinct genotype-phenotype patterns in non-syndromic hereditary hypotrichosis: a multicenter Chinese cohort. Br J Dermatol. 2026;DOI: 10.1093/bjd/ljag384.
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