X-linked Megalocornea Associated with the Novel CHRDL1 Gene Mutation p.(Pro56Leu*8).
BACKGROUND
The genetic basis of X-linked megalocornea (MGC1) was reported in 2012 to be caused by mutations in the CHRDL1 gene. We sought to confirm that mutations in CHRDL1 are associated with MGC1 in a previously unreported pedigree.


METHODS
Slit lamp examination, corneal pachymetry, corneal topography and DNA collection for screening of the CHRDL1 gene were performed for members of an affected family.


RESULTS
Examination of a woman and her four sons, ranging in age between 3 and 15 years, demonstrated horizontal corneal diameters of 14 mm in three of the four sons and a normal corneal diameter of 12 mm in the mother and other son. Central corneal thickness in the individuals with enlarged corneal diameters averaged 474 microns, compared to 604 microns in their unaffected brother. Corneal topographic imaging demonstrated an average K value of 44.4 D in the affected individuals compared with 41.6 D in their unaffected sibling. Screening of the CHRDL1 gene demonstrated the novel hemizygous frameshift mutation c.167delC (p.(Pro56Leu*8)) in exon 3 in the affected individuals and in the heterozygous state in their mother. This mutation was not present in the unaffected brother or in unrelated controls.


CONCLUSIONS
We provide the initial confirmation that X-linked megalocornea is associated with mutations in the CHRDL1 gene.
The Jules Stein Eye Institute, David Geffen School of Medicine at UCLA , Los Angeles , California.
Jonathan
J
Han
Jonathan W
JW
Young
Ricardo F
RF
Frausto
Sherwin J
SJ
Isenberg
Anthony J
AJ
Aldave
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003315:Cornea / Q000473:pathology*; D063171:Corneal Pachymetry; D019781:Corneal Topography; D005091:Exons / Q000235:genetics; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005784:Gene Amplification; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
C486602:CHRDL1 protein, human; D005136:Eye Proteins; D009419:Nerve Tissue Proteins
CHRDL1; Chordin-like 1 gene; MGC1; X-linked megalocornea