Background.Congenital atrichia with papular lesions is a rare,recessively inherited condition of total alopecia,characterized clinically by complete and irreversible hair loss,which begins shortly after birth with the...Background.Congenital atrichia with papular lesions is a rare,recessively inherited condition of total alopecia,characterized clinically by complete and irreversible hair loss,which begins shortly after birth with the development of the papular lesions of keratin-filled cysts over an extensive area of the body.Mutations in the human hairless(HR)gene have been implicated in the pathogenesis of this disorder.Objective.To search fora mutation in human HR in a family with congenital atrichia.Methods.Linkage analysis was carried out using genotyping markers closely linked to congenital atrichia locus on chromosome8p12.Subsequently,human HR was sequenced toidentify a disease-causing mutation.Results.A novel 11 bpinsertion mutation,G202(InsCTTCCCCCAGG),in exon 2 ofthe hairless gene was identified in a Pakistani consanguineous family affected by congenital atrichia.The insertion resultsin the expansion of 11 bp tandem repeat,which introducesa translational frame shift leading to downstream premature termination codon.Conclusions.This mutation is the first insertion mutation identified in the coding sequence of human HR.This extends our knowledge of mutations in HR that define the pathogenic basis of this disease.展开更多
Identification of mutations in the hairless (HR) gene in patients with atrichia with papular lesions (APL) has proven of critical importance, as it provides a basis for the differentiation between APL and alopecia uni...Identification of mutations in the hairless (HR) gene in patients with atrichia with papular lesions (APL) has proven of critical importance, as it provides a basis for the differentiation between APL and alopecia universalis. The establishment of the diagnostic criteria for APL has triggered the identification of a large number of APL patients among those suspected to suffer from alopecia universalis. This advancement has resulted in the discovery of an increasing number of hairless mutations in both consanguineous and nonconsanguineous APL families. Here, we report the identification of a homozygous mutation, 3434delC, in an APL patient of Arab-Palestinian descent. The proband is a 23-year-old female with generalized scalp and body alopecia. To confirm the diagnosis of APL and to identify the specific mutation, we sequenced the hairless gene. Sequencing of all exons of the hairless gene revealed a homozygous frameshift mutation, 3434delC, in exon 18. Interestingly, the same mutation was previously identified in an Arab-Israeli family. Our data suggest that the 3434delC mutation most likely represents a founder mutation in this geographical region.展开更多
Objective: To establish the unique and common clinical and microscopic characteristics of the alopecias associated with vitamin D-dependent rickets (VDDR) type IIA and with hairless gene mutations. Design: A comparati...Objective: To establish the unique and common clinical and microscopic characteristics of the alopecias associated with vitamin D-dependent rickets (VDDR) type IIA and with hairless gene mutations. Design: A comparative clinical, histologic, and immunohistochemical study of the alopecias in 6 patients withVDDRIIA and 4 patientswith atrichia with papular lesions (APL) and/or alopecia universalis congenita (AUC) (hereinafter “ APL/AUC” ). Main Outcome Measures: Clinical data were gathered from medical records, personal interviews, and physical examinations. Histologic and immunohistochemical studies were performed on 6 scalp punch biopsy specimens from each of the 2 studied groups. Results: The alopecias in VDDR IIA and APL/AUC showed similar clinical, histologic, and immunohistochemical features. The clinical presentation of the VDDR alopecia resembled either the APL phenotype (ie, with papules and milia) or the AUC phenotype (without papules and milia). The main histologic findings included void infundibula; absence of the lower two thirds of the hair follicles, often replaced by vertically oriented irregular epithelial structures or epithelial cysts; irregular epithelial structures, often with small cysts in the middle and lower dermis; and small, medium, and large keratinizing cysts at all levels of the dermis. The larger epithelial cysts in the upper dermis stained positively for cytokeratin (CK) 10, which suggests an infundibular derivation, whereas the remaining irregular epithelial structures and cysts in themiddle and lower dermis stained positivelymost frequently forCK17, CK19, andCD34,which suggests an outer root sheath derivation. Conclusions: The alopecias associated with VDDR IIA and with hairless gene mutations show striking clinical and microscopic similarities. Disintegration of the lower two thirds of the hair follicles seems to be the underlying defect, and a common pathogenetic pathwaymight be involved.展开更多
文摘Background.Congenital atrichia with papular lesions is a rare,recessively inherited condition of total alopecia,characterized clinically by complete and irreversible hair loss,which begins shortly after birth with the development of the papular lesions of keratin-filled cysts over an extensive area of the body.Mutations in the human hairless(HR)gene have been implicated in the pathogenesis of this disorder.Objective.To search fora mutation in human HR in a family with congenital atrichia.Methods.Linkage analysis was carried out using genotyping markers closely linked to congenital atrichia locus on chromosome8p12.Subsequently,human HR was sequenced toidentify a disease-causing mutation.Results.A novel 11 bpinsertion mutation,G202(InsCTTCCCCCAGG),in exon 2 ofthe hairless gene was identified in a Pakistani consanguineous family affected by congenital atrichia.The insertion resultsin the expansion of 11 bp tandem repeat,which introducesa translational frame shift leading to downstream premature termination codon.Conclusions.This mutation is the first insertion mutation identified in the coding sequence of human HR.This extends our knowledge of mutations in HR that define the pathogenic basis of this disease.
文摘Identification of mutations in the hairless (HR) gene in patients with atrichia with papular lesions (APL) has proven of critical importance, as it provides a basis for the differentiation between APL and alopecia universalis. The establishment of the diagnostic criteria for APL has triggered the identification of a large number of APL patients among those suspected to suffer from alopecia universalis. This advancement has resulted in the discovery of an increasing number of hairless mutations in both consanguineous and nonconsanguineous APL families. Here, we report the identification of a homozygous mutation, 3434delC, in an APL patient of Arab-Palestinian descent. The proband is a 23-year-old female with generalized scalp and body alopecia. To confirm the diagnosis of APL and to identify the specific mutation, we sequenced the hairless gene. Sequencing of all exons of the hairless gene revealed a homozygous frameshift mutation, 3434delC, in exon 18. Interestingly, the same mutation was previously identified in an Arab-Israeli family. Our data suggest that the 3434delC mutation most likely represents a founder mutation in this geographical region.
文摘Objective: To establish the unique and common clinical and microscopic characteristics of the alopecias associated with vitamin D-dependent rickets (VDDR) type IIA and with hairless gene mutations. Design: A comparative clinical, histologic, and immunohistochemical study of the alopecias in 6 patients withVDDRIIA and 4 patientswith atrichia with papular lesions (APL) and/or alopecia universalis congenita (AUC) (hereinafter “ APL/AUC” ). Main Outcome Measures: Clinical data were gathered from medical records, personal interviews, and physical examinations. Histologic and immunohistochemical studies were performed on 6 scalp punch biopsy specimens from each of the 2 studied groups. Results: The alopecias in VDDR IIA and APL/AUC showed similar clinical, histologic, and immunohistochemical features. The clinical presentation of the VDDR alopecia resembled either the APL phenotype (ie, with papules and milia) or the AUC phenotype (without papules and milia). The main histologic findings included void infundibula; absence of the lower two thirds of the hair follicles, often replaced by vertically oriented irregular epithelial structures or epithelial cysts; irregular epithelial structures, often with small cysts in the middle and lower dermis; and small, medium, and large keratinizing cysts at all levels of the dermis. The larger epithelial cysts in the upper dermis stained positively for cytokeratin (CK) 10, which suggests an infundibular derivation, whereas the remaining irregular epithelial structures and cysts in themiddle and lower dermis stained positivelymost frequently forCK17, CK19, andCD34,which suggests an outer root sheath derivation. Conclusions: The alopecias associated with VDDR IIA and with hairless gene mutations show striking clinical and microscopic similarities. Disintegration of the lower two thirds of the hair follicles seems to be the underlying defect, and a common pathogenetic pathwaymight be involved.
