Summary of <i>CHRDL1</i> mutations.

<p>(A) Schematic of CHRDL1 protein domains. The following abbreviations are used: SP, signal peptide; VWFC, von Willebrand factor, type C domain. (B) Schematic of the <i>CHRDL1</i> gene. (C) <i>CHRDL1</i> mutations previously reported in X-linked megalocornea families <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104163#pone.0104163-Webb1" target="_blank">[3]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104163#pone.0104163-Han1" target="_blank">[6]</a>. Frameshift, splicing, nonsense, missense, and whole gene deletion mutations were identified. (D) Novel <i>CHRDL1</i> mutations identified in MGC1 families in this study (Families A–J). The dagger (†) indicates Family K with MMR syndrome.</p

X-linked Megalocornea Families A–J.

<p>(A) Pedigree of Families A–G. Black shaded squares denote clinically and genetically confirmed affected males; grey shaded squares denote clinically diagnosed affected males but DNA samples were not available for testing; dotted circles denote genetically confirmed carrier females; ? = presumed carrier females but DNA samples were not available for testing; clear squares and circles denote unaffected individuals. Arrowhead indicates proband in each family. Control sequence electropherogram is shown above patient sequence. (B) Pedigree of Family H and sequence electropherogram showing a 9,033 bp deletion encompassing <i>CHRDL1</i> exon 5 and 8 bp insertion. (C) Pedigree of Families I and J. Deletion of the entire <i>CHRDL1</i> gene (exon 1 to exon 12) in the proband is shown in agarose gel images. The flanking genes, <i>RGAG1</i> and <i>PAK3</i> are present. NTC, non-template control (D) Schematic representation of presence or absence of the <i>CHRDL1</i> gene and flanking genes <i>RGAG1</i> and <i>PAK3</i> (Ensembl nomenclature hg19 genome build) in Families I and J.</p

Ocular phenotype: X-linked megalocornea patients.

<p>The following abbreviations and symbols have been used: NA = not available; HWTW = cornea horizontal diameter (white to white); IOP = intraocular pressure.</p

Novel <i>CHRDL1</i> missense mutation in a patient diagnosed with MMR.

<p>(A) Pedigree of Family K with megalocornea-mental retardation (MMR) syndrome. Squares, males; circles, females; diamonds, unknown gender; shaded, affected; dotted, carrier; clear, unaffected. Arrowhead indicates proband. Sequence electropherograms show the <i>CHRDL1</i> missense mutation c.464G>A; p.(Cys155Tyr), which segregates in Family K. (B–C) The proband at ages 3, and 6 years, respectively, presented with bilateral megalocorneae, broad forehead, bilateral epicanthic folds, a tented upper lip, and downturned corners of the mouth. (D–E) Frontal and sides of the proband at age of 10 years.</p