TY - JOUR
T1 - Mutations in the desmoglein 4 gene underlie localized autosomal recessive hypotrichosis with monilethrix hairs and congenital scalp erosions
AU - Schaffer, Julie V.
AU - Bazzi, Hisham
AU - Vitebsky, Anna
AU - Witkiewicz, Agnieszka
AU - Kovich, Olympia I.
AU - Kamino, Hideko
AU - Shapiro, Lawrence S.
AU - Amin, Snehal P.
AU - Orlow, Seth J.
AU - Christiano, Angela M.
N1 - Funding Information:
We appreciate the participation of the family members in this study, and the excellent technical assistance of Ms Helen Lam and Mr Bill Putnam. We thank Dr My Mahoney for providing the AP64 antibody. This study was supported in part by Grants USPHS NIH R01-AR44924 (A.M.C.).
PY - 2006/6
Y1 - 2006/6
N2 - Localized autosomal recessive hypotrichosis (LAH) is a recently defined disorder characterized by fragile, short, sparse hairs on the scalp, trunk, and extremities. Mutations in desmoglein 4 (DSG4), a novel member of the desmosomal cadherin family that is expressed in the hair follicle as well as the suprabasal epidermis, have been found to underlie LAH. Thus far, the allelic series includes a recurrent intragenic deletion identified in affected Pakastani kindreds and a missense mutation detected in an Iraqi family. We report three siblings of Iraqi and Iranian origin with LAH that presented with congenital scalp erosions and monilethrix-like hairs, features that have not been previously described in this disorder. Follicular hyperkeratotic papules and marked pruritus were also prominent clinical findings. Novel compound heterozygous DSG4 mutations, including a splice-site mutation and a missense mutation that disrupts a conserved calcium-binding site in the extracellular (EC)2-EC3 interface, were found to underlie the disease in this family. These observations broaden the phenotypic and genotypic spectrum of LAH, further illustrating the consequences of DSG4 dysfunction on epidermal and hair shaft integrity.
AB - Localized autosomal recessive hypotrichosis (LAH) is a recently defined disorder characterized by fragile, short, sparse hairs on the scalp, trunk, and extremities. Mutations in desmoglein 4 (DSG4), a novel member of the desmosomal cadherin family that is expressed in the hair follicle as well as the suprabasal epidermis, have been found to underlie LAH. Thus far, the allelic series includes a recurrent intragenic deletion identified in affected Pakastani kindreds and a missense mutation detected in an Iraqi family. We report three siblings of Iraqi and Iranian origin with LAH that presented with congenital scalp erosions and monilethrix-like hairs, features that have not been previously described in this disorder. Follicular hyperkeratotic papules and marked pruritus were also prominent clinical findings. Novel compound heterozygous DSG4 mutations, including a splice-site mutation and a missense mutation that disrupts a conserved calcium-binding site in the extracellular (EC)2-EC3 interface, were found to underlie the disease in this family. These observations broaden the phenotypic and genotypic spectrum of LAH, further illustrating the consequences of DSG4 dysfunction on epidermal and hair shaft integrity.
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U2 - 10.1038/sj.jid.5700237
DO - 10.1038/sj.jid.5700237
M3 - Article
C2 - 16543896
AN - SCOPUS:33745551443
SN - 0022-202X
VL - 126
SP - 1286
EP - 1291
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -