title: Gelatinous drop-like corneal dystrophy in a child with developmental delay: clinicopathological features and exclusion of the M1S1 gene.
abstract: OBJECTIVE
  Gelatinous drop-like corneal dystrophy (GDLD) is an early-onset, autosomal recessive condition characterised by amyloid deposits within the cornea. We report the histopathological and molecular genetic findings in a Caucasian child with GDLD who also exhibited global developmental delay.
  
  
  METHODS
  Bilateral lamellar keratoplasty was carried out at age 6 and 7 years. Tissue was fixed for light and electron microscopy, including immunoelectronmicroscopy. The coding region of the M1S1 gene was screened for mutations in the affected proband and available relatives, using DNA extracted from mouthwashes.
  
  
  RESULTS
  Nodular deposits, which were present subepithelially and in the central superficial stroma, stained typically for amyloid with PAS and Congo red. A nodular deposit of amyloid, together with large amounts of lactoferrin and sparse amounts of keratoepithelin (betaig-h3), was present in the central superficial stroma, causing destruction of Bowman's layer and elevation of the thinned, degenerate epithelium. Around the deposit zone, the stroma exhibited large numbers of thick filamentous proteoglycan deposits. While the affected child was homozygous for a novel A1133 C single-nucleotide polymorphism (SNP) that resulted in an aspartic acid to alanine substitution at position 173 of the M1S1 coding sequence, this polymorphism was also found at relatively high frequency in a sample of normal controls, enabling exclusion of the M1S1 gene as the disease locus.
  
  
  CONCLUSIONS
  Increased epithelial permeability in GDLD may be explained in part by an altered membrane permeability of the superficial epithelial cells. An association with developmental delay has not been reported previously.
authors.affiliation: School of Optometry and Vision Sciences, Cardiff University, UK. akhtars@cf.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Akhtar
authors.forename: A J
authors.initials: AJ
authors.lastname: Bron
authors.forename: X
authors.initials: X
authors.lastname: Qin
authors.forename: R C
authors.initials: RC
authors.lastname: Creer
authors.forename: J A
authors.initials: JA
authors.lastname: Guggenheim
authors.forename: K M
authors.initials: KM
authors.lastname: Meek
mesh_terms: D000682:Amyloid / Q000032:analysis; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003315:Cornea / Q000737:chemistry / Q000648:ultrastructure; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002658:Developmental Disabilities / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D016253:Microscopy, Immunoelectron; D010375:Pedigree; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D000682:Amyloid; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D007781:Lactoferrin; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C499380:TACSTD2 protein, human