title: Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis.
abstract: BACKGROUND
  Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin disorders. Several mutant genes have been identified in ARCI, but the association between genotype and phenotype is poorly understood.
  
  
  METHODS
  To investigate genotype-phenotype correlations in ARCI, we selected 27 patients from 18 families with specific ultrastructural features of the epidermis. The characteristic findings using electron microscopy (EM) were abnormal lamellar bodies and elongated membranes in the stratum granulosum, classified as ARCI EM type III. DNA samples from a subset of affected individuals were screened for homozygous genomic regions, and a candidate gene region was identified on chromosome 5q33. The region coincides with the ichthyin gene, previously reported as mutated in ARCI.
  
  
  RESULTS
  Mutation screening of ichthyin revealed missense or splice-site mutations in affected members from 16 of 18 (89%) families with characteristics of ARCI EM type III. In a control group of 18 patients with ARCI without EM findings consistent with type III, we identified one patient homozygous for a missense mutation in ichthyin.
  
  
  CONCLUSIONS
  Our findings indicate a strong association between ultrastructural abnormalities in the granular layer of epidermis and ichthyin mutations. The results also suggest that EM provides a tool for specific diagnosis in a genetically homogenous subgroup of patients with ARCI.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Dahlqvist
authors.forename: J
authors.initials: J
authors.lastname: Klar
authors.forename: I
authors.initials: I
authors.lastname: Hausser
authors.forename: I
authors.initials: I
authors.lastname: Anton-Lamprecht
authors.forename: M Hellström
authors.initials: MH
authors.lastname: Pigg
authors.forename: T
authors.initials: T
authors.lastname: Gedde-Dahl
authors.forename: A
authors.initials: A
authors.lastname: Gånemo
authors.forename: A
authors.initials: A
authors.lastname: Vahlquist
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D002895:Chromosomes, Human, Pair 5; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007057:Ichthyosis / Q000175:diagnosis* / Q000235:genetics*; D015603:Keratinocytes / Q000378:metabolism; D008854:Microscopy, Electron; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000235:genetics / Q000473:pathology
chemical_list: C499859:NIPAL4 protein, human; D011956:Receptors, Cell Surface