Posterior polymorphous corneal dystrophy 3 is associated with agenesis and hypoplasia of the corpus callosum.

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Posterior polymorphous corneal dystrophy (PPCD ) is a dominantly inherited disorder of the corneal endothelium that has been associated with mutations in the zinc-finger E -box binding homeobox 1 gene (ZEB 1 ) gene in approximately one -third of affected families . While the corneal dystrophies have traditionally been considered isolated disorders of the corneal endothelium , we have recently identified two cases of maldevelopment of the corpus callosum in unrelated individuals with PPCD . The proband of the first family was diagnosed shortly after birth with agenesis of the corpus callosum and several other developmental abnormalities . Karyotype , FISH and whole genome copy number variant analyses were normal . She was subsequently diagnosed with PPCD , prompting screening of the ZEB 1 gene , which identified a novel deletion (c .449 delG ; p .(Gly 150 Alafs *36 )) present in the heterozygous state that was not identified in either unaffected parent . The proband of the second family was diagnosed several months after birth with thinning of the corpus callosum and PPCD . Whole genome copy number variant analysis revealed a 1 .79 Mb duplication of 17 q 12 in the proband and her father and brother , neither of whom had PPCD . ZEB 1 sequencing identified a novel deletion (c .1913 -1914 delCA ; p .(Ser 638 Cysfs *5 )) present in the heterozygous state , which was also identified in the proband 's affected mother . Thus , we report the first two cases of the association of PPCD with a developmental abnormality of the brain , in this case maldevelopment of the corpus callosum .