Congenital atrichia with papular lesions resulting from novel mutations in human hairless gene in four consanguineous families

Abstract

Congenital atrichia with papular lesions (APL; Mendelian Inheritance in Man no. 209500) is a rare form of irreversible alopecia that follows an autosomal recessive mode of inheritance. Patients with this form of alopecia show hair loss soon after birth with the development of papular lesions of keratin-filled cysts over the body. Several studies have reported sequence variants in the human hairless (HR) gene as the underlying cause of this disorder. In the present study, we have reported four consanguineous families showing features of APL. Genotyping using microsatellite markers showed mapping of all four families to the hairless (HR) gene on chromosome 8p21.1. Further, DNA sequence analysis of the HR gene revealed three novel mutations including two nonsense (p.Cys690X, p.Arg819X) and a missense (p.Pro1157Arg) in the four families.

Congenital atrichia associated with an uncommon mutation of HR gene

“…6 Therefore our case is the second reporting such a variant, but with the distinctive feature of absence of papular lesions, so far in any of the affected siblings. This finding, in accordance with other studies, 2,3,5 emphasizes the difficulty to establish a strict correlation between HR genotyping and the phenotype. …”

“…2 Generally, the affected individuals have normal hair at birth that is then shed almost completely during the first weeks or months of life and never regrows. 2 This disorder affects equally both gender and is genetically heterogeneous, mostly caused by autosomal recessive variants in the HR gene, 2,3 although mutations in the vitamin D receptor gene have been associated with a phenotype similar to APL. 4 We emphasize the role of trichoscopy in the differential diagnosis with other forms of hair loss, especially alopecia areata universalis to avoid unnecessary treatments.…”

Atrichia with Papular Lesions in a Chinese Family Caused by Novel Compound Heterozygous Mutations and Literature Review

“…The two probands of similar age demonstrated variations in the number of papules and well-developed infundibula. On the contrary, it is intriguing that the recurrent mutations p.P1157R, p.Q323X and Q502X in 6 unrelated Pakistani families separately verified to have similar haplotype generated almost the same phenotypes [26,27]. Available evidence indicates that the common mutation 3434delC does not probably share an ancestry considering the number of papular lesions distinct from each Arab family [28,29].…”

The twisting tale of woolly hair: a trait with many causes

“…VDR is a nuclear receptor which has already been shown before to have a critical role in hair growth since patients with hereditary vitamin D resistant rickets (OMIM 277440) who harbour mutations in the VDR also have sparse hair 79. Additionally, mutations in the hairless (HR) gene, which is a corepressor for the VDR, lead to atrichia with papular lesions (OMIM 209500) 80. Together, it is apparent that regulation of hair structure is strictly controlled by a complex of proteins, involving the VDR, corepressors and coactivators.…”