Recessive cornea plana in the Kingdom of Saudi Arabia.
OBJECTIVE
To characterize the molecular genetics of clinically diagnosed recessive cornea plana in the Kingdom of Saudi Arabia and establish the presence of common or limited founders (ancestors who originally harbored the disease-causing mutation) in the country's historically isolated population.


METHODS
Prospective interventional case series.


METHODS
Twelve affected patients from apparently unrelated Saudi Arabian nuclear families with clinically diagnosed recessive cornea plana.


METHODS
Clinical ophthalmic examination and venous blood sampling for DNA sequencing.


METHODS
Age, gender, keratometry, best-corrected visual acuity, ocular alignment, cycloplegic refraction, significant findings of a complete ophthalmic examination, and keratocan gene (KERA) haplotype analysis.


RESULTS
All 12 individuals had classic phenotypic features of recessive cornea plana and were homozygous for 1 of 2 KERA mutations--a novel frameshift mutation (1634delC) or a previously reported nonsense mutation (R313X). Haplotype analysis was consistent with a separate distinct common founder effect for each instance. An additional Saudi KERA mutation (R279X) has been reported previously in one family.


CONCLUSIONS
Specific for mutation in KERA, the ophthalmic phenotype of recessive cornea plana does not significantly vary with different KERA mutations. The occurrence of a rare inherited disease in a historically isolated population is not always due to a single common founder effect; it may be explained by cultural preferences such as consanguinity (intrafamilial marriage) and endogamy (intratribal marriage), which enhance expression of recessively inherited diseases.
Khan
Arif O
AO
Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.edu
Aldahmesh
Mohammed
M
Meyer
Brian
B
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003317:Corneal Dystrophies, Hereditary / Q000453:epidemiology / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008297:Male; D008967:Molecular Biology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011509:Proteoglycans / Q000235:genetics*; D012029:Refraction, Ocular; D012529:Saudi Arabia / Q000453:epidemiology; D014792:Visual Acuity
D018389:Codon, Nonsense; D017931:DNA Primers; D005136:Eye Proteins; C490948:KERA protein, human; D011509:Proteoglycans