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.
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Acknowledgements
This work has been made possible by the Agency for Innovation by Science and Technology (IWT; SBO-60848 to JRV); Research Foundation Flanders (FWO; FWO grant G.0320.07. to JRV); University of Leuven (KU Leuven) SymBioSys (PFV/10/016 and GOA/12/015 to JRV and KD). HVE and KD received fund as a ‘Clinical Researcher’ of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO). The Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO, 1.8.012.07.N.02) and the Instituut voor Wetenschap en Technologie (IWT/070715) fund JDP as a ‘Clinical Researcher’. The programme is further supported by the Industria-Academia Partnership Marie Curie Grant of the European Commission (http://www.endovv.com; PIAP-GA-2009-251356). This research was supported by funding from the Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP) programme through the project IAP P7/43-BeMGI.
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Brady, P., Van Esch, H., Fieremans, N. et al. Expanding the phenotypic spectrum of PORCN variants in two males with syndromic microphthalmia. Eur J Hum Genet 23, 551–554 (2015). https://doi.org/10.1038/ejhg.2014.135
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DOI: https://doi.org/10.1038/ejhg.2014.135
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