title: Expanding the phenotypic spectrum of PORCN variants in two males with syndromic microphthalmia.
abstract: 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.
authors.affiliation: Center for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brady
authors.affiliation: Center for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Esch
authors.affiliation: Center for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fieremans
authors.affiliation: Center for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
authors.affiliation: Division of Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Slavotinek
authors.affiliation: 1] Department of Development and Regeneration, Unit Pregnancy, Foetus and Newborn, KU Leuven, Leuven, Belgium [2] Department Obstetrics and Gynaecology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Deprest
authors.affiliation: Center for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
authors.affiliation: Center for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
mesh_terms: D000217:Acyltransferases; D005260:Female; D005489:Focal Dermal Hypoplasia / Q000235:genetics; D014644:Genetic Variation; D023281:Genomics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D046228:Microarray Analysis; D008850:Microphthalmos / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D049951:X Chromosome Inactivation
chemical_list: D008565:Membrane Proteins; D000217:Acyltransferases; C491188:PORCN protein, human