HR – Alopecia Universalis Congenita

HR-associated alopecia universalis congenita is inherited in an autosomal recessive manner. To date, a single unrelated patient has been reported presenting with congenital, irreversible hair loss and complete atrichia. Sequence analysis identified a homozygous missense variant, c.3034G>A (p.Asp1012Asn), in exon 17 of HR which affects the thyroid hormone receptor interacting domain 2 (TRID2). The variant was present in a homozygous state in the proband and heterozygous in the mother, and absent in an unaffected sibling, consistent with recessive segregation (PMID:12406339).

Functional studies in rat models previously demonstrated that mutations in TRID2 disrupt HR binding to the thyroid receptor, implicating this domain in hair follicle regulation. However, a follow-up analysis in a human atrichia with papular lesions cohort indicated that the D1012N substitution does not significantly impair HR–thyroid receptor interaction, suggesting that additional mechanisms may underlie pathogenicity. Overall, the evidence for HR in alopecia universalis congenita remains limited, highlighting the need for further case series and functional assays to elucidate pathogenic mechanisms. Key take-home: Genetic testing of HR can confirm autosomal recessive alopecia universalis congenita and guide family counseling.

References

• The Journal of investigative dermatology • 2002 • A novel missense mutation affecting the human hairless thyroid receptor interacting domain 2 causes congenital atrichia. PMID:12406339

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