Interaction of hairless and thyroid hormone receptor is not involved in the pathogenesis of atrichia with papular lesions Karima Djabali 1 , Abraham Zlotogorski 2 , Arye Metzker 3 , Dani Ben-Amitai 4 and Angela M. Christiano 1 1 Departments of Dermatology and Genetics & Development, Columbia University, New York, NY, USA; 2 Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3 Sourasky Medical Center, Tel Aviv, Israel; 4 Rabin Medical Center, Petah-Tikva, Israel Key words: atrichia – hair follicle – hairless – mutation – thyroid hormone receptor Angela M. Christiano, PhD Department of Dermatology Columbia University College of Physicians & Surgeons 630 West 168th Street VC-1526 New York, NY 10032, USA Tel.: þ1 212 305 9565 Fax: þ1 212 305 7391 e-mail: amc65@columbia.edu Accepted for publication 18 October 2003 Djabali K, Zlotogorski A, Metzker A, Ben-Amitai D, Christiano AM. Interactionofhairlessandthyroidhormonereceptorisnotinvolvedinthe pathogenesis of atrichia with papular lesions. Exp Dermatol 2004: 13: 251–256. # Blackwell Munksgaard, 2004 Abstract: Atrichia with papular lesions (APL) (MIM 209500) is a rare autosomal recessive disease characterized by early onset of atrichia, followedbyapapulareruptionwithinthefirstyearsoflife.Recentstudies demonstrating linkage to chromosome 8p21 and further mutation detectioninthehairlessgene(HR)haveestablishedthemolecularbasisof APL. This study describes the case of a 16-year-old female with APL due to a missense mutation, D1012N, in the hr–thyroid hormone receptor interacting domain 2 (TRID2) of the HR. Using functional and biochemical analysis, it was determined that this mutation does not significantly affect hr-thyroid hormone receptor interaction. This result suggests that the TRID2 domain either is dispensable in the hr–TR interaction or is not involved in the pathogenesis of APL. Introduction Atrichia with papular lesions (APL) (MIM 209500)isarareautosomalrecessivediseasechar- acterized by early onset of atrichia, followed by a papular eruption within the first years of life. Recent studies demonstrating linkage to chromo- some8p21(1–3)andfurthermutationdetectionin the hairless gene (HR) have established the mole- cular cause of this disease by documenting mis- sense, nonsense, deletion, insertion and splice-site mutations in the HR gene from patients around theworld(4–14).IncreasedawarenessofAPLand the finding of patients mistakenly diagnosed with alopecia universalis led to the establishment of criteria to properly diagnose APL (12). These cri- teriaincludeapatternofinheritanceestablishedas autosomal recessive with possible history of con- sanguinity.Patientsarebornwithouthairor,more typically, born with normal hair that sheds after several months and never regrows, except for sparse eyebrows and eyelashes. Papules begin to appear during the first years of life, particularly underthemidlineoftheeye,onthefaceandextrem- ities. The laboratory findings include: (i) lack of response to any treatment modality; (ii) biopsy demonstrating absence of hair follicle structures and the presence of cysts filled with cornified mater- ial; and (iii) associated mutation(s) in the hr gene. Theneedforthesecriteriaisunderscoredbythe confusion in nomenclature which led to designa- tion of two names to the same disease originating frommutationsinthe HR gene:APLandalopecia universalis congenita (AUC) (MIM 203655). Although the history, clinical examination and Experimental Dermatology 2004: 13: 251–256 Copyright # Blackwell Munksgaard 2004 Blackwell Munksgaard . Printed in Denmark EXPERIMENTAL DERMATOLOGY ISSN 0906-6705 251