Study of p.N247S KERA mutation in a British family with cornea plana.
OBJECTIVE
To report clinical and genetic findings in a white British family with autosomal recessive cornea plana (CNA2) with a negative history for consanguinity. To look for evidence of a common ancestry with previously reported Finnish CNA2 patients by studying haplotypes.


METHODS
Clinical examination and direct sequencing of the keratocan (KERA) gene was performed in two siblings affected with CNA2 and one unaffected parent. We also studied 22 single nucleotide polymorphisms distributed in the KERA genomic region by direct sequencing in this family as well as in one additional Finnish patient with CNA2 and 24 white British control subjects.


RESULTS
Both siblings had the homozygous c.740A>G mutation leading to a p.N247S amino acid change originally reported as the founder mutation in 35 Finnish families. Genetic characterization of genomic regions surrounding the gene revealed large linkage disequilibrium, but the presence of shared extended haplotypes between affected individuals from Finland and the United Kingdom is consistent with a recent common ancestor.


CONCLUSIONS
This is the first description of recessive cornea plana in a white British family and it is the second report on the p.N247S change in the KERA gene. Extended haplotype analysis suggests that the two geographically remote occurrences of the c.740A>G mutation may have a common origin.
Liskova
Petra
P
Division of Molecular Genetics, Institute of Ophthalmology, UCL, London, UK. p.liskova@ucl.ac.uk
Hysi
Pirro G
PG
Williams
Denise
D
Ainsworth
John R
JR
Shah
Sunil
S
de la Chapelle
Albert
A
Tuft
Stephen J
SJ
Bhattacharya
Shomi S
SS
D000328:Adult; D001216:Asparagine / Q000235:genetics*; D016022:Case-Control Studies; D003316:Corneal Diseases / Q000235:genetics* / Q000473:pathology; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics*; D012694:Serine / Q000235:genetics*; D006113:United Kingdom; D044465:White People / Q000235:genetics*
C490948:KERA protein, human; D011509:Proteoglycans; D012694:Serine; D001216:Asparagine