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

Abstract

Background: Congenital atrichia with papular lesions (APL) is characterized by complete absence of body hair shortly after birth, along with papules, and caused by mutations in the hairless gene (HR). Objective: To investigate whether APL with HR mutations might also be found among patients in non-consanguineous Chinese families and to discuss the phenotypic variations with the same mutations. Methods: DNA sequencing of the HR was performed in the Chinese pedigree and in 100 controls. Results: A nonsense mutation c.T2265A in the patient and his father as well as a 2bp deletion (3482delCT) in the patient and his mother were detected. Conclusion: Our study identified the first mutation in exon 10 in HR as well as the second novel compound heterozygous mutations in a Chinese family, also adding new variants to the knowledge of HR mutations in APL. Phenotypic heterogeneity in congenital atrichia might be subject to the founder genes or modifier genes.

Identification of a recurrent nonsense mutation in HR gene responsible for atrichia with papular lesions in two Kashmiri families

“…In the present study, we investigated two consanguineous families originating from different ethnic groups settled in Azad Jammu and Kashmir. The clinical features observed in affected members of the families were similar to those reported earlier . Whole exome sequencing of both families led to identification of recurrent nonsense (NM_005144: c.2818C > T; p.Arg940*) mutation in exon 13 of the human hairless gene ( HR ).…”

Atrichia with papular lesions: A case report

“…Published estimates of APL prevalence remain low, despite having the pathogenetic mutations in HR identified in distinct populations around the world, often affected by consanguinity. [2][3][4][6][7][8][9][10][11][12][13][14][15][16][17] It is suspected to be more common than current estimates, as APL is often mistaken for autoimmune AU, achieving the diagnosis after patients fail to respond to standard treatment modalities. 2,18 In APL, hairs are typically absent from the scalp, axillae, and body, and individuals are almost completely devoid of eyebrows and eyelashes.…”

“…6 Although the majority of cases of APL involve homozygous mutations, sporadic cases of compound heterozygous mutations in nonconsanguinous families have been identified over the past decade. 10,17 The differential diagnosis of APL includes AU, congenital hypotrichosis, vitamin D-dependent rickets type II (same phenotype, mutation in the VDR), and ectodermal dysplasia. 2,16 Consanguinity, the development of AU within the first year of life, disseminated cysts or papules, and nonresponsiveness to therapy strongly suggests the diagnosis of APL.…”

“…Published estimates of APL prevalence remain low, despite having the pathogenetic mutations in HR identified in distinct populations around the world, often affected by consanguinity. 2 – 4 , 6 – 17 It is suspected to be more common than current estimates, as APL is often mistaken for autoimmune AU, achieving the diagnosis after patients fail to respond to standard treatment modalities. 2 , 18 …”

“… 6 Although the majority of cases of APL involve homozygous mutations, sporadic cases of compound heterozygous mutations in nonconsanguinous families have been identified over the past decade. 10 , 17 …”