Microcephaly-capillary malformation syndrome: Brothers with a homozygous STAMBP mutation, uncovered by exome sequencing

Am J Med Genet A. 2016 Nov;170(11):3018-3022. doi: 10.1002/ajmg.a.37845. Epub 2016 Aug 17.

Abstract

We describe two brothers from a consanguineous family of Egyptian ancestry, presenting with microcephaly, apparent global developmental delay, seizures, spasticity, congenital blindness, and multiple cutaneous capillary malformations. Through exome sequencing, we uncovered a homozygous missense variant in STAMBP (p.K303R) in the two siblings, inherited from heterozygous carrier parents. Mutations in STAMBP are known to cause microcephaly-capillary malformation syndrome (MIC-CAP) and the phenotype in this family is consistent with this diagnosis. We compared the findings in the present brothers with those of earlier reported patients. © 2016 Wiley Periodicals, Inc.

Keywords: MIC-CAP; STAMBP; exome sequencing; microcephaly-capillary malformation syndrome.

MeSH terms

  • Brain / pathology
  • Capillaries / abnormalities*
  • Consanguinity
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Endosomal Sorting Complexes Required for Transport / genetics*
  • Exome
  • Facies
  • Genetic Association Studies
  • High-Throughput Nucleotide Sequencing
  • Homozygote*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Microcephaly / diagnosis*
  • Microcephaly / genetics*
  • Mutation
  • Pedigree
  • Phenotype
  • Siblings
  • Syndrome
  • Ubiquitin Thiolesterase / genetics*
  • Vascular Malformations / diagnosis*
  • Vascular Malformations / genetics*

Substances

  • Endosomal Sorting Complexes Required for Transport
  • STAMBP protein, human
  • Ubiquitin Thiolesterase

Supplementary concepts

  • Capillary Malformations, Congenital, 1

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