A non-mosaic PORCN mutation in a male with severe congenital anomalies overlapping focal dermal hypoplasia.

TitleA non-mosaic PORCN mutation in a male with severe congenital anomalies overlapping focal dermal hypoplasia.
Publication TypeJournal Article
Year of Publication2017
AuthorsMadan, S, Liu, W, Lu, JT, V Sutton, R, Toth, B, Joe, P, Waterson, JR, Gibbs, RA, Van den Veyver, IB, Lammer, EJ, Campeau, PM, Lee, BH
JournalMol Genet Metab Rep
Volume12
Pagination57-61
Date Published2017 Sep
ISSN2214-4269
Abstract

Mutations in the PORCN gene cause the X-linked dominant condition focal dermal hypoplasia (FDH). Features of FDH include striated pigmentation of the skin, ocular and skeletal malformations. FDH is generally associated with in utero lethality in non-mosaic males and most of the currently reported male patients show mosaicism due to de novo post-zygotic mutations in the PORCN gene. There is only one previous report of a surviving male with an inherited mutation in the PORCN gene. Here, we report two male siblings with multiple malformations including skeletal, ocular and renal defects overlapping with FDH. A novel PORCN mutation (p.Ser250Phe) was identified in a non-mosaic, hemizygous state in one of the siblings who survived to 8 years of age. The mother is a heterozygous carrier, has a random X-inactivation pattern and is asymptomatic. Findings unusual for FDH include dysplastic clavicles and bilateral Tessier IV facial clefts. This is the second case report of a non-mosaic PORCN mutation in a male individual with multiple congenital anomalies. While the pathogenicity of this mutation remains to be further investigated, the survival of a male with a non-mosaic mutation in PORCN is suggestive of a functionally mild mutation leading to an X-linked recessive mode of inheritance.

DOI10.1016/j.ymgmr.2017.06.002
Alternate JournalMol Genet Metab Rep
PubMed ID28626639
PubMed Central IDPMC5466597