Expanding the phenotypic spectrum of PORCN variants in two males with syndromic microphthalmia

Paul D Brady, Hilde Van Esch, Nathalie Fieremans, Guy Froyen, Anne Slavotinek, Jan Deprest, Koenraad Devriendt, Joris R Vermeesch

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Variants in PORCN are a cause of Goltz-Gorlin syndrome or Focal Dermal Hypoplasia, an X-linked dominant disorder affecting heterozygous females and until now considered to be embryonic lethal in males. Exome sequencing was performed in a family in which two male siblings were characterized by microphthalmia and additional congenital anomalies including diaphragmatic hernia, spina bifida and cardiac defects. Surprisingly, we identified a maternally inherited variant in PORCN present in both males as well as in two female siblings. This represents the first finding of a PORCN variant in non-mosaic males affected with Goltz-Gorlin syndrome. The apparently asymptomatic mother showed extreme skewing of X-inactivation (90%), an asymptomatic female sibling showed skewing of 88%, and the second female sibling affected with cutis aplasia of the scalp showed X-inactivation considered within the normal range.

Original languageEnglish
Pages (from-to)551-4
Number of pages4
JournalEuropean Journal of Human Genetics
Issue number4
Publication statusPublished - Apr 2015


  • Acyltransferases
  • Female
  • Focal Dermal Hypoplasia/genetics
  • Genetic Variation
  • Genomics
  • Humans
  • Male
  • Membrane Proteins/genetics
  • Microarray Analysis
  • Microphthalmos/diagnosis
  • Pedigree
  • Phenotype
  • Sequence Analysis, DNA
  • X Chromosome Inactivation


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