HR and Hypotrichosis 4

A heterozygous missense mutation in HR (c.974G>A (p.Gly325Asp)) was identified in a 68-year-old Hungarian woman presenting with alopecia universalis and limb deformities, expanding the phenotypic spectrum of hypotrichosis 4. Direct sequencing showed the variant in the proband and one affected family member, with the unaffected son and unrelated controls carrying the wild-type allele, consistent with autosomal dominant inheritance (PMID:22584530).

The mutation lies in exon 3 of HR, a gene encoding a transcriptional corepressor critical for hair follicle cycling. No functional assays were conducted for p.Gly325Asp; however, an autosomal recessive Gly960Trp mutation in mouse Hr causes early-onset irreversible hair loss, wrinkled skin, and nail defects, supporting a crucial role for HR in hair maintenance (PMID:16455232).

No additional segregation or functional data are available for c.974G>A in humans. Further investigation is required to confirm pathogenicity and to clarify the molecular mechanism of limb deformities in conjunction with hair loss. Key take-home: Screening of HR should be considered in unexplained cases of autosomal dominant hypotrichosis.

References

• Archives of dermatological research • 2012 • A newly identified missense mutation of the HR gene is associated with a novel, unusual phenotype of Marie Unna Hereditary Hypotrichosis 1 including limb deformities. PMID:22584530
• Genomics • 2006 • A novel missense mutation in the mouse hairless gene causes irreversible hair loss: genetic and molecular analyses of Hr m1Enu. PMID:16455232

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