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Researchers have taken an important step to understanding keratoconus (KC), a common reason for corneal transplantation in the developed world. They did so with the first scan of the whole genome in different races, identifying a new locus likely to be responsible for a significant proportion of cases of isolated familial KC.
Genotyping followed by linkage analysis in a small sample of families suggested linkage on chromosome 2p for marker D2S305 but not to chromosomes 16q, 18p, or 21q, previously suggested for familial KC. Typing the full complement of 28 families for 36 other markers across an 80 cM region spanning D2S319 and D2S286 suggested linkage at D2S305. Further analysis suggested significant linkage to 2p24. Marker alleles segregated at 2p24 in affected members in 17 of the 28 families, and the locus for KC was placed in a 1.69 Mb region, within which were two intervals common to all 17. None of the five known genes in the two intervals yet has a known role in human disease, but research is continuing into the expression of all candidate genes
The families were of Caucasian, Arabic, or Caribbean African descent. Among the 253 family members at least two per family had the disorder. The cause of KC is still unknown. The familial form accounts for 6–10% of cases. Mostly it seems to show autosomal dominant inheritance, though autosomal recessive and, rarely, X linked inheritance has been claimed. Various other loci have been mooted—in restricted, homogeneous populations—maybe pointing to genetic heterogeneity.
Hutchings H, et al. Journal of Medical Genetics 2005;42:88–94.