title: Two Japanese familial cases of Caffey disease with and without the common COL1A1 mutation and normal bone density, and review of the literature.
abstract: Caffey disease, also known as infantile cortical hyperostosis, is a rare bone disease characterized by acute inflammation with swelling of soft tissues and hyperostosis of the outer cortical surface in early infancy. The common heterozygous mutation of the COL1A1 gene, p.Arg1014Cys, has been reported in patients with Caffey disease. However, its pathogenesis remains to be elucidated, and the reason for the incomplete penetrance and transient course of the disease is still unclear. In the present study, we performed mutation analysis of the COL1A1 and COL1A2 genes and measured bone mineral density in two Japanese familial cases of Caffey disease. The index case and two clinically healthy members of one family carry the common heterozygous mutation; in contrast, no mutation in COL1A1 or COL1A2 was identified in the affected members of the second family. In addition, we found normal bone mineral density in adult patients of both families who have had an episode of cortical hyperostosis regardless of the presence or absence of the common p.Arg1014Cys mutation.
  
  
  CONCLUSIONS
  The results reveal that Caffey disease is genetically heterogeneous and that affected and unaffected adult patients with or without the common COL1A1 mutation have normal bone mineral density.
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kitaoka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Namba
authors.forename: Kohji
authors.initials: K
authors.lastname: Miura
authors.forename: Takuo
authors.initials: T
authors.lastname: Kubota
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohata
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Masaki
authors.initials: M
authors.lastname: Takagi
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
mesh_terms: D015502:Absorptiometry, Photon; D044466:Asian People; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006958:Hyperostosis, Cortical, Congenital / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain