Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia

Am J Med Genet A. 2010 Nov;152A(11):2875-9. doi: 10.1002/ajmg.a.33621.

Abstract

Knobloch syndrome (KNO) is caused by mutations in the collagen XVIII gene (COL18A1) and patients develop encephalocele and vitreoretinal degeneration. Here, we report an El Salvadorian family where two sisters showed features of KNO. One of the siblings also developed acute lymphoblastic leukemia. DNA sequencing of COL18A1 revealed a homozygous, 2-bp deletion (c3514-3515delCT) in exon 41, which leads to abnormal collagen XVIII and deficiency of its proteolytic cleavage product endostatin. KNO patients with mutations in COL18A1 may be at risk for endostatin-related conditions including malignancy.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Child
  • Child, Preschool
  • Collagen Type XVIII / genetics*
  • DNA Mutational Analysis
  • Encephalocele / complications
  • Encephalocele / genetics
  • Eye Abnormalities / genetics
  • Family
  • Female
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Retinal Degeneration
  • Retinal Detachment / complications
  • Retinal Detachment / congenital
  • Retinal Detachment / genetics

Substances

  • Collagen Type XVIII

Supplementary concepts

  • Knobloch syndrome