Posterior polymorphous corneal dystrophy 3 is associated with agenesis and hypoplasia of the corpus callosum.
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 (ZEB1) 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 ZEB1 gene, which identified a novel deletion (c.449delG; p.(Gly150Alafs*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 17q12 in the proband and her father and brother, neither of whom had PPCD. ZEB1 sequencing identified a novel deletion (c.1913-1914delCA; p.(Ser638Cysfs*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.
The Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Michelle S
MS
Jang
The Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Ashley N
AN
Roldan
The Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Ricardo F
RF
Frausto
The Jules Stein Eye Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. Electronic address: aldave@jsei.ucla.edu.
Anthony J
AJ
Aldave
D000015:Abnormalities, Multiple; D000293:Adolescent; D061085:Agenesis of Corpus Callosum / Q000235:genetics / Q000473:pathology*; D002675:Child, Preschool; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics / Q000473:pathology*; D003337:Corpus Callosum / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
Agenesis; Corneal dystrophy; Corpus callosum; PPCD3; ZEB1; ZEB2