Study of p.N247S KERA mutation in a British family withcornea plana

[摘要] Purpose: To report clinical and genetic findings in a white Britishfamily with autosomal recessive cornea plana (CNA2) with a negativehistory for consanguinity. To look for evidence of a common ancestrywith previously reported Finnish CNA2 patients by studying haplotypes.Methods: Clinical examination and direct sequencing of thekeratocan (KERA) gene was performed in two siblings affectedwith CNA2 and one unaffected parent. We also studied 22 singlenucleotide polymorphisms distributed in the KERA genomic region bydirect sequencing in this family as well as in one additional Finnishpatient with CNA2 and 24 white British control subjects.Results: Both siblings had the homozygous c.740A>G mutationleading to a p.N247S amino acid change originally reported as thefounder mutation in 35 Finnish families. Genetic characterization ofgenomic regions surrounding the gene revealed large linkagedisequilibrium, but the presence of shared extended haplotypes betweenaffected individuals from Finland and the United Kingdom is consistentwith a recent common ancestor.Conclusions: This is the first description of recessive cornea planain a white British family and it is the second report on the p.N247Schange in the KERA gene. Extended haplotype analysis suggests thatthe two geographically remote occurrences of the c.740A>G mutationmay have a common origin.

[学科分类] 生物化学/生物物理