Molecular genetic analysis in autosomal dominant keratoconus.
Members in three generations of a family whose propositus had keratoconus were examined by biomicroscopy, with a corneoscope and a computer-assisted videophoto-keratoscope. Keratoconus was detected in eight of 15 family members with vertical transmission consistent with autosomal dominant inheritance. Affected individuals displayed variable topographic features. Abortive "nipple-type" cones were identified in some individuals in successive generations using the computer-assisted videophotokeratoscope and more advanced nipple-type cones detected on biomicroscopy of other family members. We selected a COL6A1 cDNA (the gene encoding the alpha 1 chain of type VI collagen) as a "candidate gene" to determine cosegregation with the disease locus. Linkage analysis excluded a gene locus for keratoconus on the most telomeric region of chromosome 21 in this family.
Rabinowitz
Y S
YS
Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland.
Maumenee
I H
IH
Lundergan
M K
MK
Puffenberger
E
E
Zhu
D
D
Antonarakis
S
S
Francomano
C A
CA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002891:Chromosomes, Human, Pair 21; D003094:Collagen / Q000235:genetics; D004247:DNA / Q000032:analysis; D015342:DNA Probes; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007640:Keratoconus / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008967:Molecular Biology; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D015342:DNA Probes; D003094:Collagen; D004247:DNA