title: Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly.
abstract: OBJECTIVE
  Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations.
  
  
  METHODS
  We screened for COL4A1 mutations in 61 patients with porencephaly and 10 patients with schizencephaly, which may be similarly caused by disturbed vascular supply leading to cerebral degeneration, but can be distinguished depending on time of insult.
  
  
  RESULTS
  COL4A1 mutations were identified in 15 patients (21%, 10 mutations in porencephaly and 5 mutations in schizencephaly), who showed a variety of associated findings, including intracranial calcification, focal cortical dysplasia, pontocerebellar atrophy, ocular abnormalities, myopathy, elevated serum creatine kinase levels, and hemolytic anemia. Mutations include 10 missense, a nonsense, a frameshift, and 3 splice site mutations. Five mutations were confirmed as de novo events. One mutation was cosegregated with familial porencephaly, and 2 mutations were inherited from asymptomatic parents. Aberrant splicing was demonstrated by reverse transcriptase polymerase chain reaction analyses in 2 patients with splice site mutations.
  
  
  CONCLUSIONS
  Our study first confirmed that COL4A1 mutations are associated with schizencephaly and hemolytic anemia. Based on the finding that COL4A1 mutations were frequent in patients with porencephaly and schizencephaly, genetic testing for COL4A1 should be considered for children with these conditions.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan..
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Yoneda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Haginoya
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokochi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arai
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Takamichi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Otsuki
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Takahito
authors.initials: T
authors.lastname: Wada
authors.forename: Norihisa
authors.initials: N
authors.lastname: Koyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Mino
authors.forename: Noriko
authors.initials: N
authors.lastname: Kondo
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirabayashi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Takanashi
authors.forename: Akihisa
authors.initials: A
authors.lastname: Okumura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kumagai
authors.forename: Satori
authors.initials: S
authors.lastname: Hirai
authors.forename: Makoto
authors.initials: M
authors.lastname: Nabetani
authors.forename: Shinji
authors.initials: S
authors.lastname: Saitoh
authors.forename: Ayako
authors.initials: A
authors.lastname: Hattori
authors.forename: Mami
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Kumakura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sugo
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Satoko
authors.initials: S
authors.lastname: Miyatake
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Doi
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
mesh_terms: D000743:Anemia, Hemolytic / Q000235:genetics / Q000473:pathology; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000172:deficiency / Q000235:genetics*; D006429:Hemiplegia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D054220:Malformations of Cortical Development / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D065708:Porencephaly
chemical_list: C547475:COL4A1 protein, human; D024141:Collagen Type IV