title: Allelic and locus heterogeneity in autosomal recessive gelatinous drop-like corneal dystrophy.
abstract: Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive disease characterized by the deposition of amyloid beneath the corneal epithelium and by severely impaired visual acuity leading to blindness. Although gelatinous corneal dystrophy has previously been mapped to chromosome 1p and seems to be associated with mutations in the M1S1 gene, molecular genetic studies have been limited to Japanese patients. To investigate the cause of GDLD in patients with diverse ethnic backgrounds, we performed linkage analyses in eight unrelated GDLD families from India, USA, Europe, and Tunisia. In seven of these families, the disease locus mapped to a 16-cM interval on the short arm of chromosome 1 between markers D1S519 and D1S2835, a region including the M1S1 gene. In addition, a 1.2-kb fragment containing the entire coding region of M1S1 gene was sequenced in affected individuals. Seven novel mutations (M1R, 8-bp ins., Q118 E, V194 E, C119 S, 870delC, and 1117delA) were identified in six families and two unrelated individuals. No sequence abnormalities were detected in a single family in which the GDLD locus was also excluded from the M1S1 region by linkage analysis. These findings demonstrate allelic and locus heterogeneity for GDLD.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Md. 20892-1860, USA.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ren
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Lin
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Klintworth
authors.forename: Fumino
authors.initials: F
authors.lastname: Iwata
authors.forename: Francis L
authors.initials: FL
authors.lastname: Munier
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: Leila
authors.initials: L
authors.lastname: El Matri
authors.forename: Veena
authors.initials: V
authors.lastname: Theendakara
authors.forename: Surendra
authors.initials: S
authors.lastname: Basti
authors.forename: Madhukar
authors.initials: M
authors.lastname: Reddy
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
mesh_terms: D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003241:Consanguinity; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D000071858:Epithelial Cell Adhesion Molecule; D005060:Europe; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007194:India; D007781:Lactoferrin / Q000235:genetics; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D014416:Tunisia; D014481:United States
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D005819:Genetic Markers; D004247:DNA; D007781:Lactoferrin