De novo p.G696S mutation in COL4A1 causes intracranial calcification and late-onset cerebral hemorrhage: A case report and review of the literature COL4A1-associated vasculopathy

Keishiro Kinoshita, Yoshito Ishizaki, Hiroyuki Yamamoto, Motoshi Sonoda, Kousuke Yonemoto, Ryutaro Kira, Masafumi Sanefuji, Akihiko Ueda, Hirotaka Matsui, Yukio Ando, Yasunari Sakai, Shouichi Ohga

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

Background: The collagen type IV alpha 1 chain (COL4A1) is an essential component of the basement membrane in small vessels. Pathogenic variants in COL4A1 cause perinatal cerebral hemorrhages in an autosomal-dominant fashion. However, little is known about the long-term outcomes of patients with mildly affecting COL4A1 mutations. Case report: We report a 17-year-old boy, who presented with recurrent intracranial hemorrhages in the periventricular white matter. He had been followed-up as a child with cerebral palsy bearing intracranial calcifications, developmental delay and epilepsy. Screening tests in infancy provided negative results for intrauterine infections. Severe motor and cognitive deficits persisted after admission. Carbazochrome was introduced on day 19 of admission, which appeared to prevent extension and reactivation of cerebral hemorrhages for over 6 months after discharge. Results: Targeted sequencing of NOTCH3 and TREX1 excluded causal mutations in these genes. The whole-exome sequencing revealed that he carried a de novo mutation in COL4A1 (p.Gly696Ser). An overview of the literature for 345 cases with COL4A1 mutations supported evidence that p.Gly696Ser is associated with the unique phenotype of late-onset hemorrhage among patients with COL4A1-associated cerebral angiopathy. Conclusions: This case first demonstrates that infants with COL4A1-associated leukoencephalopathy and calcifications have a risk for developing the rupture of small vessels in the cerebral white matter after 10 years of age.

本文言語英語
論文番号103825
ジャーナルEuropean Journal of Medical Genetics
63
4
DOI
出版ステータス出版済み - 4 2020

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)

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