title: Heavy-chain amyloidosis in TGFBI-negative and gelsolin-negative atypical lattice corneal dystrophy.
abstract: OBJECTIVE
  An atypical case of late-onset lattice corneal dystrophy is described in a 61-year-old man without a family history of eye disease. Mutational analysis of the TGFBI gene excluded any pathogenic sequence variants. However, 2 years later, renal impairment and nephrotic syndrome were diagnosed, resulting in a diagnosis of systemic heavy-chain amyloidosis.
  
  
  METHODS
  Slit-lamp examination, corneal photography, and in vivo confocal microscopy were performed. General systemic evaluation included blood and urine assessment, bone marrow and renal biopsies, and cardiologic evaluation. A DNA sample underwent initial mutational analysis of TGFBI and, subsequently, gelsolin. The renal biopsy sample was subject to direct protein sequencing by mass spectrometry.
  
  
  RESULTS
  A bilateral, atypical, fine, midperipheral lattice corneal dystrophy with minor central subepithelial scarring was clinically characterized. Subsequently, abnormal renal functions with proteinuria, IgG lambda paraproteinemia, extensive deposition of amyloid in renal glomeruli, and increased plasma cells in bone marrow were identified. No pathogenic sequence mutations were identified in TGFBI or the gelsolin genes. Direct protein sequencing by mass spectrometry showed amyloid to be heavy-chain deposition rather than the more usual light-chain deposition.
  
  
  CONCLUSIONS
  Atypical midperipheral lattice corneal dystrophy presenting with adult onset and negative family history should arouse suspicion for an association with paraproteinemias or amyloidosis. Exclusion of TGFBI mutations should alert the clinician to the possibility of potentially life-threatening conditions, with referral for careful systemic evaluation.
authors: Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, New Zealand.
authors: Monika A
authors: MA
authors: Pradhan
authors: Ross A
authors: RA
authors: Henderson
authors: Dipika
authors: D
authors: Patel
authors: Charles N J
authors: CN
authors: McGhee
authors: Andrea L
authors: AL
authors: Vincent
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D004252:DNA Mutational Analysis; D003907:Dexamethasone / Q000627:therapeutic use; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D018260:Gelsolin / Q000235:genetics*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D008297:Male; D013058:Mass Spectrometry; D008558:Melphalan / Q000008:administration & dosage; D018613:Microscopy, Confocal; D008875:Middle Aged; D009154:Mutation; D009404:Nephrotic Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D010265:Paraproteinemias / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D011719:Pyrazines / Q000008:administration & dosage; D020539:Sequence Analysis, Protein; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D000682:Amyloid; D001897:Boronic Acids; D000069286:Bortezomib; D003907:Dexamethasone; D016326:Extracellular Matrix Proteins; D018260:Gelsolin; D005938:Glucocorticoids; D007143:Immunoglobulin Heavy Chains; D008558:Melphalan; D011719:Pyrazines; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein