title: Novel CDH3 mutations in hypotrichosis with juvenile macular dystrophy.
abstract: BACKGROUND
  Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse and short hair, heralding progressive degeneration of the retinal pigment epithelium, which leads to blindness by the second decade of life. The disorder is caused by mutations in CDH3, a gene encoding P-cadherin, a major component of adherens junctions. Most HJMD cases reported to date have been shown to be caused by homozygous CDH3 mutations segregating in consanguineous families.
  
  
  OBJECTIVE
  To elucidate the genetic basis of HJMD in two nonconsanguineous families, we established the coding sequence of CDH3 in four patients and their healthy siblings.
  
  
  RESULTS
  The four patients demonstrated markedly variable degrees of visual acuity impairment. Novel biallelic recessive mutations were identified in all affected individuals. One patient in the first family was found to carry two heterozygous mutations, IVS2 + 1G-->A and p.E504K; the other three patients in the second family were compound heterozygous for a missense mutation, p.H575R, and a nonsense mutation, p.R221X.
  
  
  CONCLUSIONS
  This paper expands the spectrum of known mutations in CDH3 and points to the existence of clinical heterogeneity in this syndrome.
authors.affiliation: Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Indelman
authors.forename: J
authors.initials: J
authors.lastname: Eason
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: O
authors.initials: O
authors.lastname: Loza
authors.forename: M
authors.initials: M
authors.lastname: Suri
authors.forename: M J
authors.initials: MJ
authors.lastname: Leys
authors.forename: M
authors.initials: M
authors.lastname: Bayne
authors.forename: F L
authors.initials: FL
authors.lastname: Schwartz
authors.forename: E
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D000293:Adolescent; D015820:Cadherins / Q000235:genetics*; D002648:Child; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: C512197:CDH3 protein, human; D015820:Cadherins