Madan Simran, Liu Wei, Lu James T, Sutton V Reid, Toth Bryant, Joe Priscilla, Waterson John R, Gibbs Richard A, Van den Veyver Ignatia B, Lammer Edward J, Campeau Philippe M, Lee Brendan H
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA.
Mol Genet Metab Rep. 2017 Jun 7;12:57-61. doi: 10.1016/j.ymgmr.2017.06.002. eCollection 2017 Sep.
Mutations in the 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 lethality in non-mosaic males and most of the currently reported male patients show mosaicism due to post-zygotic mutations in the gene. There is only one previous report of a surviving male with an inherited mutation in the gene. Here, we report two male siblings with multiple malformations including skeletal, ocular and renal defects overlapping with FDH. A novel 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 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 is suggestive of a functionally mild mutation leading to an X-linked recessive mode of inheritance.
