Autosomal recessive corneal endothelial dystrophy (CHED2) is associated with mutations in SLC4A11.
OBJECTIVE
To map and identify the gene for autosomal recessive congenital hereditary endothelial dystrophy (CHED2, OMIM 217700), a disorder characterised by diffuse bilateral corneal clouding that may lead to visual impairment and requiring corneal transplantation.


METHODS
Members of 16 families with autosomal recessive CHED were genotyped for 13 microsatellite markers at the CHED2 locus on chromosome 20p13-12. Two-point linkage analysis was carried out using the FASTLINK version of the MLINK program. Mutation screening was carried out by amplification of exons and flanking regions by polymerase chain reaction, followed by direct automated sequencing.


RESULTS
Linkage and haplotype analysis placed the disease locus within a 2.2 cM (1.3 Mb) interval flanked by D20S198 and D20S889, including SLC4A11. The maximum LOD score of 11.1 was obtained with D20S117 at theta = 0. Sequencing of SLC4A11 showed homozygotic mutations in affected members from 12 of 16 families.


CONCLUSIONS
These results confirm that mutations in the SLC4A11 gene cause autosomal recessive CHED.
Jiao
Xiaodong
X
Sultana
Afia
A
Garg
Prashant
P
Ramamurthy
Balasubramanya
B
Vemuganti
Geeta K
GK
Gangopadhyay
Nibaran
N
Hejtmancik
J Fielding
JF
Kannabiran
Chitra
C
D027321:Anion Transport Proteins / Q000235:genetics*; D017920:Antiporters / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003241:Consanguinity; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree
D027321:Anion Transport Proteins; D017920:Antiporters; C425809:SLC4A11 protein, human