title: Mutations in the desmoglein 4 gene are associated with monilethrix-like congenital hypotrichosis.
abstract: The gene encoding human desmoglein 4 (DSG4) was recently cloned, and a mutation in this gene has been reported in several consanguineous Pakistani families affected with localized autosomal recessive hypotrichosis (LAH). In addition, various mutations in the Dsg4 gene have been identified in animal models of hypotrichosis that share a characteristic phenotype called "lanceolate hair". To date, the features of the hair-shaft anomaly in patients with LAH have not been well described. We report a Japanese patient affected with congenital hypotrichosis that was originally diagnosed as monilethrix because she had a hair-shaft abnormality that resembled moniliform hair. However, no mutations were found in the type II hair keratin genes, hHb1, hHb3, and hHb6, whose mutations cause monilethrix. Instead, we identified novel compound heterozygous mutations in the DSG4 gene of our patient. On the maternal allele is a novel S192P transition within the extracellular cadherin II domain of DSG4; on the paternal allele is a novel 2039insT mutation leading to the generation of unstable transcripts. Here we present the observation that mutations in the DSG4 gene can cause monilethrix-like congenital hypotrichosis. Based on our findings, we propose that LAH and monilethrix could overlap.
authors.affiliation: Department of Dermatology, Niigata University School of Medicine, Niigata, Japan. yshimo@med.niigata-u.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sakamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kariya
authors.forename: Kayoko
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ito
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D051182:Desmogleins / Q000235:genetics*; D005260:Female; D006197:Hair / Q000648:ultrastructure*; D006201:Hair Diseases / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics* / Q000473:pathology; D007633:Keratins / Q000235:genetics; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009154:Mutation; D020871:RNA Stability; D014158:Transcription, Genetic
chemical_list: C473409:DSG4 protein, human; D051182:Desmogleins; D007633:Keratins