title: Structural and molecular hair abnormalities in trichothiodystrophy.
abstract: We examined hair from 15 patients with trichothiodystrophy (TTD), a rare inherited disorder with brittle, cystine-deficient hair. They had a wide variety of phenotypes, from brittle hair only to severe intellectual impairment and developmental delay. Polarizing light microscopic examination showed alternating light and dark (tiger tail) bands under polarizing microscopy. Confocal microscopy captured structural features of breaks in intact TTD hairs. The autofluorescent appearance was regular and smooth in normal donors and markedly irregular in sections of TTD hairs possibly reflecting abnormalities in melanin distribution. Scanning electron microscopy revealed numerous surface irregularities. All TTD hair samples had reduced sulfur content. We observed an inverse correlation (R(val)=0.9) between sulfur content and percent of hairs with shaft abnormalities (trichoschisis, trichorrhexis nodosa, or ribbon/twist). There was no association between clinical disease severity and percent of abnormal hairs. Raman spectra of hairs from TTD patients and normal donors revealed a larger contribution of energetically less favored disulfide conformers in TTD hairs. Our data indicate that the brittleness of the TTD hair is dependent upon abnormalities at several levels of organization. These changes make TTD hairs excessively prone to breakage and weathering.
authors.affiliation: DNA Repair Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4258, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Liang
authors.forename: Andrea
authors.initials: A
authors.lastname: Morris
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schlücker
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imoto
authors.forename: Vera H
authors.initials: VH
authors.lastname: Price
authors.forename: Emory
authors.initials: E
authors.lastname: Menefee
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Wincovitch
authors.forename: Ira W
authors.initials: IW
authors.lastname: Levin
authors.forename: Deborah
authors.initials: D
authors.lastname: Tamura
authors.forename: Katrin R
authors.initials: KR
authors.lastname: Strehle
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
authors.forename: John J
authors.initials: JJ
authors.lastname: DiGiovanna
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006197:Hair / Q000002:abnormalities* / Q000648:ultrastructure; D006201:Hair Diseases / Q000473:pathology*; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D013059:Spectrum Analysis, Raman; D013455:Sulfur / Q000032:analysis / Q000172:deficiency*
chemical_list: D013455:Sulfur