title: Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection.
abstract: BACKGROUND
  A clinical case is described of growth retardation, severe developmental delay, facial dysmorphic features with microcephaly, as well as congenital cataract, schizencephaly, periventricular calcifications, and epilepsy.
  
  
  METHODS
  TORCH infection was suspected, but all tests for toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus were negative for the child and her mother; however, an increased level of antibodies against parvovirus B19 was detected in the proband.
  
  
  RESULTS
  Chromosomal analysis and array-CGH showed no aberration. Target capture sequencing for COL4A1 and COL4A2 revealed a de novo COL4A1 mutation (c.2123G>T [p.Gly708Val]). The mutation occurred at a highly conserved Gly residue in the Gly-X-Y repeat of the collagen triple helical domain, suggesting that these mutations may alter the collagen IV α1α1α2 heterotrimers. The mutation was predicted to be damaging.
  
  
  CONCLUSIONS
  We suggest that COL4A1 testing should be considered in patients with schizencephaly as well as with phenotype suggesting TORCH infection without any proven etiological factors.
authors.affiliation: Department of Social Pediatrics, Wroclaw Medical University, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Smigiel
authors.affiliation: Department of Social Pediatrics, Wroclaw Medical University, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cabala
authors.affiliation: Department of Genetics, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jakubiak
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kodera
authors.affiliation: Department of General and Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Sasiadek
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Genetics, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Sasiadek
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
mesh_terms: D057215:Body Dysmorphic Disorders / Q000235:genetics / Q000473:pathology; D002386:Cataract / Q000235:genetics / Q000473:pathology; D024141:Collagen Type IV / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010322:Parvoviridae Infections; D016732:Parvovirus B19, Human; D065707:Schizencephaly / Q000235:genetics / Q000473:pathology
chemical_list: C547475:COL4A1 protein, human; D024141:Collagen Type IV
keywords: COL4A1; Schizencephaly; cataract; congenital infection; developmental delay; periventricular calcifications