A new CUL4B variant associated with a mild phenotype and an exceptional pattern of leukoencephalopathy

Am J Med Genet A. 2017 Oct;173(10):2803-2807. doi: 10.1002/ajmg.a.38390. Epub 2017 Aug 17.

Abstract

Cabezas type of X-linked syndromic intellectual disability (MRXSC; MIM300354) is a rare X-linked recessive intellectual disability characterized primarily by intellectual disability, short stature, hypogonadism, and gait abnormalities. It is caused by a wide spectrum of hemizygous variants in CUL4B. In a 10-year-old boy with an exceptional leukoencephalopathy pattern, we identified a new missense variant p.Leu329Gln in CUL4B using "Mendeliome" sequencing. However, his phenotype does not include the severe characteristics currently known for MRXSC. We discuss the divergent phenotype and propose a potential connection between the different CUL4B variants and corresponding phenotypes in the context of the current literature as well as 3D homology modeling.

Keywords: CUL4B; Cabezas type; cullin 4B; gait abnormalities; leukoencephalopathy; white matter lesion.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Cullin Proteins / genetics*
  • Humans
  • Leukoencephalopathies / genetics*
  • Leukoencephalopathies / pathology
  • Male
  • Mutation, Missense*
  • Phenotype
  • Prognosis

Substances

  • CUL4B protein, human
  • Cullin Proteins