title: NIPAL4/ichthyin is expressed in the granular layer of human epidermis and mutated in two Pakistani families with autosomal recessive ichthyosis.
abstract: BACKGROUND
  Autosomal recessive congenital ichthyosis (ARCI) can be divided into 3 types including lamellar ichthyosis (OMIM 242304), nonbullous congenital ichthyosiform erythroderma (OMIM 242100) and harlequin ichthyosis (OMIM 242500). The last type is uncommon since newborns with harlequin ichthyosis usually die shortly after birth. Several genes have been linked to ARCI, but these represent only 60% of the known genetic causes of this condition.
  
  
  METHODS
  After having performed a linkage analysis, we analyzed the DNA of 2 consanguineous Pakistani families with ARCI for NIPAL4 mutations and performed in situ hybridization (ISH) for NIPAL4 mRNA in the epidermis.
  
  
  RESULTS
  The haplotype analysis revealed a linkage to chromosome 5, and we identified a recurrent missense mutation, p.A176D, in affected individuals from both families. We also determined by ISH that NIPAL4 mRNA is highly expressed in the granular cell layer of the epidermis, consistent with the ARCI phenotype.
  
  
  CONCLUSIONS
  Our results expand the spectrum of the clinical manifestations of the NIPAL4 gene and further extend our understanding of its molecular function.
authors.affiliation: Department of Dermatology, Columbia University, New York, NY 10032, USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.forename: Mazen
authors.initials: M
authors.lastname: Kurban
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: C499859:NIPAL4 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface